Abnormal Result

Potassium of 1.9 mmol/L was found on a blood gas analysis.

Presenting Complaint

Patient presented with a few isolated episodes of muscle weakness. This progressed from 2 weeks before, during the index episode, to become so severe that he couldn’t walk.

History

Patient was given IV potassium + MgSO4 upon which the potassium normalised to 5.5 mmol/L
History of muscle weakness was on and off over the last few months – unable to walk for brief periods of time.
No Family Hx of illnesses / hypokalmeia
No hypertension and no family Hx of hypertension
Patient had sweating more than usual. No other overt Sx of hyperthyroidism.
No medications

The mother had no similar symptoms ever.

The father was unfortunately not involved and not contactable.

Examination

Normal pulses
Small goiter, diffusely enlarger
No cardiovascular system abnormalities

Laboratory Investigations

Potassium upon the current consultation: 4.6 mmol/L
Normal Sodium, Creatinine, calcium, magnesium, phosphate and chloride

Normal pH 7.35
Normal HC03
Suspecting: Hypokalemic periodic paralysis
TSH < 0.01
Free T4: 59 pmol/L
Free T3: 21 pmol/L
TSH-Receptor Antibodies: Increased above the cut-off

Creatine Kinase 749

Other Investigations

The further investigations needed to confirm the diagnosis

Final Diagnosis

Considering the fact that the patient had no renal tubular acidosis, no medication which could cause the low potassium, it was, according to the endocrinologist, likely a diagnosis of Thyrotoxic Periodic Paralysis (TPP).

Patient was placed on Neomercazole and a Beta-adrenergic receptor blocker.

Take Home Message

I wasn’t aware of the condition until this case was brought up to the endocrinology meeting.

Thyrotoxic periodic paralysis is a rare cause of muscle paralysis.

TPP is a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis.

It has been increasingly reported in the USA due to the rise in the immigrant population. Hypokalemia in TPP results from an intracellular shift of potassium induced by the thyroid hormone sensitization of Na⁺/K⁺–ATPase rather than depletion of total body potassium. Treatment of TPP includes prevention of this shift of potassium by using nonselective beta-blockade, correcting the underlying hyperthyroid state, and replacing potassium.

It is important for physicians to distinguish TPP from familial hypokalemic periodic paralysis, a more common cause of periodic paralysis in Caucasians. The absence of a family history of paralysis, male sex, presentation in the second to fourth decades of life, and signs of thyrotoxicosis like sinus tachycardia help in the diagnosis of this disorder. Early recognition of TPP is vital to initiating appropriate treatment and to avoiding the risk of rebound hyperkalemia that may occur if high-dose potassium replacement is given.

It is most common in Asian populations – incidence approximately 2% in patients with thyrotoxicosis of any cause.

It has been recognized in Thais, Filipinos, Vietnamese, Koreans, Malaysians, Hispanics, African Americans, and Caucasians. It is characterized by acute onset of severe hypokalemia and profound proximal muscle weakness in patients with thyrotoxicosis.

Abnormal Result

49yr old female

Presenting Complaint

Medical complaint: Suspected Conn’s disease – right adrenal lesion/ irregular left adrenal gland

History

Past Medical History: Resistant Hypertension, primary hyperaldosteronism (confirmed previously with saline infusion test), hypokalaemia, hypercholesterolaemia, newly diagnosed DM.

Family History: Hypertension – Mother.

Past Surgical History: TAH – 7 years ago.

Allergies: Nil known

Smoker

Meds: Amlodipine/Valsartan 10/320 daily, Doxazosin 8mg daily, Furosemide 40mg daily, Spironolactone 25mg daily, Carvedilol 25mg daily, Metformin 1g nocte, Simvastatin 20mg nocte, Zolpidem 10mg nocte.

Examination

Not available

Laboratory Investigations

Other Investigations

Not available for this patient.

Ideally one would need a CT with contrast beforehand to adequately visualize the positions of the adrenal veins, as this may aid in the canulation, especially of the right adrenal vein.

One needs to diagnose hyperaldosteronism (by an appropriate salt loading test) before proceeding to bilateral adrenal vein sampling.

Final Diagnosis

Interpretation

Selectivity index

Right: 0.2 (mean)

Left: 2.8 (mean)

These two results indicate that the left adrenal has likely been canulated adequately, but the right vein inadequately.

Lateralization index

Unable to comment because of the inadequate canulation of the right adrenal vein. If determined, it would very likely provide a false result.

Contralateral suppression index

616.8 /1260.25 : 2540/3609

= 0.70

This falls in between some of the referenced cutoffs (<1 and <0.5)

All of the other samples also fall somewhere in this range. Biochemically, these results suggests inadequate right sided venous sampling (a commonly described problem)

Take Home Message

• Procedure is done in the Cath Lab
• The patient received continuous synacthen infusion
• Done under imaging with contrast used for the localisation of the adrenal gland and adrenal vein
• Sequential sampling technique used, generally > 20 mins infusion
• Multi-disciplinary: nurses, anaesthetist, radiographer, intervention radiologists, students, chemical pathologists
• Difficulty with sampling right side for both patients
• Difficulty with interpreting results – most likely due to inadequate canulation of the right adrenal vein

Some important learning points

1. Adrenal vein sampling may be a valuable tool that is underutilised
2. Careful selection of patients essential – also patient should consent to surgical removal of the affected adrenal before this invasive procedure is initiated
3. Inter-disciplinary approach is necessary
4. Obtaining cosyntroponin (aka synacthen) can be difficult (Section 21), but recommended
5. Right adrenal access difficult: may require specific imaging. Recommended to start on the right or do simulataneous sampling
6. Adrenalectomy may be curative or help achieve better control of BP thus decrease associated morbidity and mortality in those with unilateral adenoma

Abnormal Result

TSH: < 0.01 mIU/L (0.27 – 4.2)

Free-T4: 80.9 pmol/L (12 -22)

Free-T3: 10.8 pmol/L (3.1 – 6.8)

Presenting Complaint

Started to have frequent supra-ventricular arythmias – hence placed on amiodarone by the cardiologists

History

Mitral valve repair in 2018.

Started Warfarin, then later stopped.

Upon routine visit for follow-up 1 w before, the cardiologist requested TFT’s.

Examination

• Denies chest pain, shortness of breath and has no symptoms of dyspnoea
• No lower limb oedema
• No sweating
• No abdominal complaints
• Patient is comfortable, no distress
• CVS unremarkable
• Muffled systolic murmur, JVP normal, No lower limb oedema.
• Fine tremor, pulse rate 84
• No eye signs
• Gland diffusely enlarged, and no focal nodules detected
• Bruit was clearly audible

Laboratory Investigations

TSH receptor antibodies = 3.3 U/L (<1.8)

Other Investigations

Radio-active Iodine thyroid uptake scan showed no uptake in the thyroid gland – not indicative of Graves Thyrotoxicosis.

Final Diagnosis

Summary: 21 y female, 1 y after mitral valve replacement placed on amiodarone now presented with a diffusely enlarged thyroid gland with a bruit clearly audible and no signs or symptoms of hyperthyroidism, but with biochemical evidence of significant hyperthyroidism

DDx: No symptoms pointing towards overt thyroid problems before initiating, thus this is likely Amiodarone – induced thyrotoxicosis

2 types are known, differentiated by either a diffusely enlarged thyroid which is more likely type 2 than type 1 .

Take Home Message

Rx differs between type 1 and type 2:

High iodine uptake is usually type 1 : usual Rx of Hyperthyroidism is given, thus Lugol’s iodine, else if non-responsive: radio-active Iodine or surgery.

If not much uptake on the uptake scan: Type 2 : points towards destruction of the gland : Rx = steroids

Which is more common?

In a local study of ~250 patients in 10y period it was found the longer it is left, the higher the chance of thyrotoxicosis. “Type 2 is likely more common”- prof Ross.

How does lithium thyroid disease work?

Lithium increases the enterothyroidal iodine recirculation : characteristically causing a : goiter with hypo or hyperthyroidism (thyroiditis).

Lithium inhibits proteases which liberates T3 and T4, hence inhibiting Iodine recirculation.

Interestingly, despite having a free T4 of ~80pmol/L, the patient had no symptoms whatsoever.

Also, of note, amiodarone more often causes hyperthyroidism than hypothyroidism.

Abnormal Result

Prolactin 51.1 ug/L

Monomeric Prolactin 36.2 ug/L

Presenting Complaint

Amenorrhoea (more details unknown)

History

The patient presented with a tempoparietal tumour and had received two episodes of radiotherapy – was asked by the oncologists to be reviewed by the Endocrinologists.

Mother stopped epilim (reason unknown)

Patient currently has amenorrhoea (unknown whether it is primary or secondary)

Examination

Residual right hemiplegia

Unfortunately no other facts about the physical examination are known

Laboratory Investigations

• Normal TFT:
  • TSH 1.7 mIU/L (0.51 – 4.3)
  • Free T4 16.2 (12.6 – 21.0)
• Cort 11am 330 nmol/L
• FSH 3.8 IU/L
• LH 2.4 IU/L
• E3 106 pmol/L
• Prol 51.1 ug/L
• Monomeric Prolactin 36.2 ug/L
• Recovery: 70.8%

Other Investigations

Proposed investigations:

• Pregnancy test (most common cause of amenorrhoea)
• Ovarian ultrasound to exclude early-onset PCOS (which may become a diagnosis of exclusion)
• History about prior amenorrhoea
• Brain MRI to visualize pathology in the cranium

Final Diagnosis

Hyperprolactinemia – likely causing amenorrhoea – cause yet to be determined

Take Home Message

Hyperprolactinemia is perhaps one of the most common problems in clinical endocrinology. It relates with various aetiologies (see below), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through “stalk effect”) are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause.

The main physiological causes of hyperprolactinemia:

• Ovulation
• Pregnancy
• Breastfeeding
• Stress
• Exercise
• Nipple stimulation or chest wall injury

Pathological

• Prolactin-secreting pituitary adenoma
• “Stalk-effect” from sellar / parasellar lesions
• Renal failure
• Liver cirrhosis
• Primary hypothyroidism
• Polycystic Ovarian Syndrome
• Seizures

Pharmacological

• Antipsychotics / neuroleptics
• Antidepressants
• Antiemetics
• Opioids
• Antihypertensives

It is clear in this case that the history is quite important in any patient in whom hyperprolactinemia is detected, since a vast array of causes exist.

For an excellent review on prolactin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947286/

For another case of high prolactin see:

Abnormal Result

Abnormal inexplicable lauging spells: Gelastic seizures

Presenting Complaint

The patient, a 5y female presented to the medical emergency departement with status epilepticus, more accurately described as gelastic seizures: laughing for no apparent reason.

These seizures was eventually controlled with multiple anti-convulsants: 2 doses of midazolam, phenobarbital and a loading dose of phenytoin. The seizures have resolved just before the clinicians wanted to initiate Lucrin.

History

No previous medical history of note. This was the first presentation of the child to hospital with disease.

Examination

Unusual findings:

• Tanner III breasts – confirmed by an Endocrinologist
• Height Taller than +2 z-scores
• Bone age 8y

Laboratory Investigations

LH pending (expected to be high)

FSH pending (expected to be high)

E3 pending (expected to be high due to stimulation from above via GnRH)

Other Investigations

CT brain was ordered swiftly, and a hamartoma in the hypothalamic region of the brain was visualized.

Final Diagnosis

Precocious puberty – most likely due to the Tanner III breasts

Hypothalamic hamartoma (HH) – likely the focus of the epileptic episode (gelastic seizure) as well as the cause of the precocious puperty.

Take Home Message

Gelastic seizures is the term used to describe focal or partial seizures with bouts of uncontrolled laughing or giggling. They are often called laughing seizures. The person may look like they are smiling or smirking.

New to me was that HH’s are often associated with producing LH or GnRH itself:

The most common, and usually the only, endocrine disturbance in patients with HH and epilepsy is central precocious puberty (CPP). The mechanism for CPP associated with HH may relate to ectopic generation and pulsatile release of gonadotropin-releasing hormone (GnRH) from the HH, but this remains an unproven hypothesis. Possible regulators of GnRH release that are intrinsic to HH tissue include the following: (1) glial factors (such as transforming growth factor α – TGFα) and (2) γ-aminobutyric acid (GABA)–mediated excitation. Both are known to be present in surgically-resected HH tissue, but are present in patients with and without a history of CPP, suggesting the possibility that symptoms related to HH are directly associated with the region of anatomic attachment of the HH to the hypothalamus, which determines functional network connections, rather than to differences in HH tissue expression or pathophysiology.

Abnormal Result

Abnormal lipid profile (see below)

Presenting Complaint

A 73 year old female was investigated with a full lipid profile after presenting with an increased total cholesterol upon routine screening at her general practitioner.

History

The patient had an increased Total Cholesterol, but was otherwise not unwell. Medication history unfortunately not available.

Examination

Not available

Laboratory Investigations

Other Investigations

To rule out the possibility of interferents, the following tests were performed.

Final Diagnosis

Increased HDL which may likely be an APOC3 deficiency.

Take Home Message

Although not present in this case, elevated apolipoprotein B (ApoB) confers increased risk of atherosclerotic cardiovascular disease, even in a context of acceptable LDL cholesterol concentrations. Extremely low values of ApoB (<48 mg/dL) are usually related to malabsorption of food lipids and can lead to polyneuropathy. Reduced apolipoprotein A1 (ApoA1) confers an increased risk of coronary artery disease. Extremely low ApoA1 (<20 mg/dL) is suggestive of liver disease or a genetic disorder. Elevated ApoB:ApoA1 ratio confers increased risk of atherosclerotic cardiovascular disease, independently of LDL and HDL cholesterol concentrations.

If the inverse of the above is true, then this lady is likely destined to live forever, but that’s the whole conundrum in lipid metabolism – the inverse of one’s theories does not always hold true under randomized controlled studies, and due to the difficulty of finding a proper control group. It was however previously demonstrated that patients with ApoC3 deficiency (if this is the cause in this case) increases longevity.

APOC3 has been established as an inhibitor for lipoprotein lipase, a gene that hydrolyzes triglycerides to generate free fatty acids before their uptake by muscle and adipose tissue (reviewed in Jong et al). Mice with a high-level expression of human APOC3 on a background of Ldlr deficiency proved to be an excellent model for familial combined hyperlipidemia, because they are disturbed in the breakdown of triglycerides. In contrast, mice lacking Apoc3 show increased activity of LPL, which causes hypotriglyceridemia and protection from postprandial hypertriglyceridemia. From these mice studies, it became clear that a deficiency of APOC3 could cause a healthier lipoprotein profile, which is associated with protection from cardiovascular diseases. However, in the absence of APOC3-deficient subjects, this hypothesis was difficult to test directly.

Dodacki, A., Wortman, M., Saubaméa, B. et al. Expression and function of Abcg4 in the mouse blood-brain barrier: role in restricting the brain entry of amyloid-β peptide. Sci Rep 7, 13393 (2017). https://doi.org/10.1038/s41598-017-13750-0

Abnormal Result

Patient presented with Diabetic Ketoacidosis and a glucose value of 27.4 mmol/L.

Presenting Complaint

Signs and symptoms typical of Diabetic Ketoacidosis

History

Patient was diagnosed with diabetes 7 years ago after presenting with diabetic ketoacidosis. Upon diagnosis he was given insulin in the hospital. Upon discharge he was given Metformin and Glimeperide (oral hypoglycemic medication – reason for oral agents unknown – likely because of his young age?). Defaulted Rx completely. Presented with DKA again. Restarted about 2 y ago on insulin.

The differential diagnosis at the current presentation is thus one of:

1. Ketosis prone diabetes
2. LADA (Latent auto-immune diabetes of the adult)
3. Type1 – went into honeymoon phase after diagnosis and now relapsed

To differentiate – the clinicians prompted to do antibodies, insulin levels and a glucagon stimulation c-peptide dynamic test.

Examination

N/A

Laboratory Investigations

Other Investigations

A glucagon-stimulated C-peptide level was drawn.

Final Diagnosis

LADA – latent autoimmune diabetes of the adult

Take Home Message

Serum c-peptide has traditionally been thought to be an inconvenient method as immediate lab analysis is required before degradation (when collected in serum gel or plain sample tubes). This is because c-peptide is a small linear peptide, which is susceptible to enzyme proteolytic cleavage. Gel tubes are therefore traditionally required to be transported to the lab on ice, promptly centrifuged and separated, then stored in frozen conditions unless lab analysis is possible at that center.

However, c-peptide sample collection for c-peptide determination in whole blood in EDTA prepared tubes is stable at room temperature for up to 24 h. Venous blood c-peptide levels can be measured in the random, fasting, or stimulated scenarios. Random samples are taken at any time during the day without consideration of recent food intake, whereas fasting samples are taken after an 8- to 10-h fast.

Stimulation methods include using

• glucagon
• intravenous/oral glucose
• tolbutamide
• sulfonylurea
• glucose-like peptide 1
• amino acids
• a mixedmeal

In this case a glucagon stimulation yielded sufficient results to assist the clinicians in making the diagnosis, indeed a case of atypical diabetes presentation.

Abnormal Result

TSH > 100

Free T4: 0.5 pmol/L

Presenting Complaint

Patient was brought to the ER being lethargic.

History

Term Neonate; Had a history of profound jaundice after birth, with unconjugated hyperbilirubinemia.

The patient’s mother lives in Athlone, gave birth at Carl Bremer hospital where a cord blood TSH was done, but results not available at the time.

Examination

No overt abnormalities on examination was found, except the single sign of jaundice.

No defects at the base of the tongue was observed.

No abnormalities in the neck was observed.

Laboratory Investigations

TSH > 100

Free T4: 0.5 pmol/L

Other Investigations

The patient had an ultrasound of the abdomen done (since it was the first occurence of hyperbilirubinemia, and in fact is termed pathological jaundice).

Cord blood TSH was retrospectively reviewed as being 178 uIU/ml.

Final Diagnosis

Congenital hypothyroidism

Take Home Message

Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with congenital hypothyroidism may show no symptoms, or may display mild symptoms that often go unrecognized as a problem. Significant deficiency may cause lethargy, hypotonia, hoarse cry, infrequent bowel movements, significant jaundice, and hypothermia.

Causes of congenital hypothyroidism include

• iodine deficiency (most common cause)
• developmental defect in the thyroid gland, either due to a genetic defect or a biochemical defect in thyroxine production
• pituitary defects – congenital hypopituitarism (present at birth) may be the result of complications around delivery, or may be the result of insufficient development (hypoplasia) of the gland, sometimes in the context of specific genetic abnormalities.

Abnormal Result

Fingerprick glucose 2.9 mmol/L

Presenting Complaint

Hypoglycemic seizure

History

The patient is a known type 1 diabetic patient who presented to the Internal Medicine Paediatric specialist OPD during two occasions of hypoglycemic seizures before.

The pateint had, according to the mothed, no post-ictal state.

She was admitted to the Endocrinology ward for a fast provocation test. At two hours, the glucose measured 2.9mM on point-of-care glucometer – glucose and other parameters on laboratory values however is illustrated below.

2 weeks after this presentation patient presented again with hypoglycemic seizures – mother is a nurse – puts in drip after which the patient’s condition normalizes.

IGF-1 normal, Ketones raised (quantitative beta-hydroxybutyrate, Insulin: 6 nmol/L, glucose: 3.5mM, hGH: 1.9 ug/L.

Examination

On examination the patient had no signs and symptoms of hypoglycemia (during the provocative test). And after the hypoglycemic seizure there were no “post-ictal” symptoms identified.

Laboratory Investigations

Glucose 3.5 mmol/L /L
Insulin: 6 nmol/L
Lactate 1.5 mmol/L (0.5 – 2.2)
Beta-hydroxybutyrate 1855 umol/L (20 – 270)
Ammonia 56 umol/L (11 – 35)
Cortisol 367 nmol/L
Cortisol reference intervals (when performed on a Roche Cobas analyzer):
Levels in adults: Morning (06:00-10:00) 133 – 537 nmol/L ; Afternoon (16:00-20:00) 68 – 327 nmol/L
Human growth hormone 1.9 ug/L

IGF-1 (Insulin-like growth factor I) @ 22/02/2021 09:30 : 366.0 ug/L (170.0 – 527.0)
Tanner stages Boys vs Girls:
Stage I 63 – 271 ug/L ; 71 – 394 ug/L
Stage II 114 – 411 ug/L ; 122 – 508 ug/L
Stage III 166 – 510 ug/L ; 164 – 545 ug/L
Stage IV 170 – 456 ug/L ; 174 – 480 ug/L
Stage V 161 – 384 ug/L ; 169 – 400 ug/L

Synacthen stimulation test:

Other Investigations

Final Diagnosis

Type 1 Diabetes with ketoacidosis and occasional episodes of hypoglycemia

Possible reasons for the hypoglycemia may be:

1. Ketogenic diet (fairly easily excludable I think).
2. Ketone utilisation disorder:

• SCOT (succinyl-CoA:3-ketoacid CoA transferase) deficiency
• Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency

Take Home Message

There are two predominant ketone utilisation disorders: SCOT deficiency and beta-ketothiolase deficiency. These disorders produce fairly continuous ketones, as they cannot be metabolised in the muscle and brain upon these deficiencies, which are autosomal recessive (as is most inherited metabolic diseases).

Giving the mother a urine dipstick home to measure urine at home mane before meals, midday just before meals and late afternoon or so before meals may be advised to assist with the diagnosis of one of the above disorders.

Urine organic acid analysis can sometimes pick up a marker to diagnose beta-ketothiolase deficiency:

Abnormal Result

Salivary Cortisol = 36 nmol/L

Presenting Complaint

Struggling with a right hand abscess – seen at the hand surgeons for the abscess. She ascribed this hand abscess due to “easy bruising”.

The patient is stable but feeling generally unwell with proximal muscle weakness.

Reported symptoms of depression.

History

In 2017 a pituitatry microadenoma was diagnosed after the patient presented with weight gain, moon facies, easy bruising and being weak proximally.

The Cushings disease is ACTH – dependent (determined with a DDAVP stimulation test – see below).

The patient was known to Endocrinology and Neurosurgery departments and unfortunately had lost two of her booked surgery dates for transsphenoidal petrosal sinus sampling due to the COVID pandemic. She was then

Hypertension on ACEi, HCTZ, Amlodipine

Examination

On this visit the patient was found to have proximal muscle weakness, and had signs and symptoms of a severe depressive episode.

Laboratory Investigations

Midnight salivary cortisol 36.00 nmol/L

        Salivary cortisol reference intervals (when performed on a Roche Cobas
        analyzer):

        Reference Range:
         Morning   (06:00 - 10:00)  < 24.10 nmol/L
         Afternoon (16:00 - 20:00)  < 9.65  nmol/L
         Midnight +/- 30 minutes    < 11.30 nmol/L

        Ref: Cobas package insert

Other Investigations

CT Scan in 2017 confirmed a microadenoma of the pituitary gland (<1cm)

From figure 1, a 37.6% increase in cortisol is observed (722 to 994 nmol/L).

Final Diagnosis

ACTH- dependent Cushings Syndrome (Cushings Disease). The patient was initiated on Ketokonazole, an antifungal which has shown to decrease cortisol in some patients in a multicenter study where they mention it’s “worth a try” (J Clin Endocrinol Metab. 2014 May;99(5):1623-30. doi: 10.1210/jc.2013-3628). The liver enzymes in this patient didn’t increase significantly (not shown).

The patient does get intermittent hypokalemia (2.9mM the morning of presentation) but the clinicians are hesitant to start on spironolactone. Potassium was being replaced. One of the Endocrinologists (Dr Bill Toet) also advised stopping the HCTZ since it may worsen hypokalemia

Depression – likely related to the hypercortisolism – patient was initiated on fluoxetine.

Take Home Message

Thiazide diuretics increase the excretion of sodium, chloride, and water by inhibiting sodium ion transport across the renal tubular epithelium. Although thiazides may have more than one action, the major mechanism responsible for diuresis is to inhibit active chloride reabsorption at the distal portion of the ascending limb or, more likely, the early part of the distal tubule (i.e., the cortical diluting segment). Exactly how chloride transport is impaired is unknown. Thiazides also increase the excretion of potassium and bicarbonate, and they decrease the urinary excretion of calcium and uric acid. Hydrochlorothiazide may be used to reduce hypercalciuria and prevent the recurrence of calcium-containing renal calculi. By increasing the sodium load at the distal renal tubule, hydrochlorothiazide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Hypochloremia and hypokalemia can cause mild metabolic alkalosis.

Salivary Cortisol: The cortisol concentration in saliva is 10-fold lower than total serum cortisol and accurately reflects the serum concentration, both levels being lowest around midnight.  A meta-analysis for 11 studies analysed, found mean sensitivity and specificity of the salivary cortisol assay were both >90%. This analysis confirms the reliability of the saliva cortisol assay as pragmatic tool for the accurate diagnosis of Cushing syndrome. 

Close monitoring of liver enzymes is necessary when patients are initiated on ketokonazole, as it is prone to cause hepatitis.

Abnormal Result

Persistent hyponatremia

2018 supracellar JPA (Astrocytoma)

Seizures – phenobarb.

Chemo @ 8 y of age.

Vincristin and Carboplatin administration

Craniospinal radiation – leptospinal

Presenting Complaint

Seizures – controlled with Phenobarbital

History

This is an 11 year old patient with a suprasellar JPA (Juvenile Pilocytic Astrocytoma). The tumour was diagnosed at 8y of age, upon which chemotherapy with Vincristine and Carboplatin was initiated. The pituitary was close to the area of radiation therapy as well.

Examination

The patient’s hydration status was normal and there was no cerebral edema.

Laboratory Investigations

The patient was found to have hypothyroidism and started on T4 replacement 50ug mane.

Other Investigations

Urine electrolytes on 23/02/2021:

• Na 54 mM
• K 31.3 mM
• Cl 110 mM
• Osmol 554 mOsmol
• Fractional reabsorption of phosphate: 85%

Final Diagnosis

Unknown – but likely indicates a tubular loss of sodium due to the chemotherapeutic agent(s).

Take Home Message

Chemotherapeutic agents does cause tubulopathy.

TMP/GFR is likely a better indicator of renal phosphate handling than only fractional reabsorption of phosphate. This can be calculated mathematically or read from a nomogram.

Abnormal Result

Glucose of < 0.1 mmol/L in a healthy individual being compos mentis.

Presenting Complaint

The patient is following up for routine check-up concerning possible hyperglycemia.

History

The mother is a known diabetic on treatment.

Examination

N/A

Laboratory Investigations

Other Investigations

The condition of the collection tubes were confirmed. All were taken in the correct collection tubes (Sodium Fluoride tubes) and appears to be correctly labelled.

Final Diagnosis

The conclusion from above findings are the following:

1. Not enough NaF was present in the sample to adequately inhibit glycolysis, enabling a falsely decreased glucose reading in the older samples (>12 hours old).
2. The patient wasn’t aware that the powder should stay in the tube when blood is collected, hence discarded the powder before taking her capillary blood samples.

Take Home Message

• Microtainer (R) specimen containers can be identified without the caps by the colour of the writing on the outside of the tube (in this case grey – the same colour as the cap).
• The presence of the correct collection tube does not equal the presence of the additive.
• Attention to detail is necessary to solve cause and effect in some cases.
• In this case the nursing staff in the Antenatal clinic was informed about the powder in the collection tubes which should not be discarded. The nurse whom I spoke to was completely unaware that the powder in the collection tube served any function.
• Glucose measurement from capillary blood samples, as in this case, can likely be inaccurate due to many possible pre-analytical (or analytical) reasons. It is however still likely a valid alternative to a resource-constrained setting, especially in South Africa, where patients cannot afford their own glucometers or where there are shortages of handheld glucometers, or more importantly, glucose measuring sticks (or cartridges).

Abnormal Result

Serum Sodium of 124 mmol/L

Presenting Complaint

A 64 year old female, presented to the Emergency unit at Khayelitsha Hospital with worsening hyponatremia.

History

The patient had a prior cholecystectomy 6 weeks ago. Histology thereon has shown chronic cholelithiasis but it was complicated with a polyp in the galbladder and adenocarcinoma thereof (completely excised during the cholecystectomy).

Examination

Not available

Laboratory Investigations

Other Investigations

Liver enzymes were normal at the last measurement (23 January), inflammatory markers normal, COVID-PCR negative on 11/01/2021.

Unfortunately neither the volume status, serum nor urine osmolarity was available on this patient’s history.

Final Diagnosis

Urinary sodium loss in one form or another. The appropriate response in hyponatremia is to decrease urinary sodium loss. In this patient, the urinary sodium was 31 (should ideally be <20 mmol/L in hyponatremia).

Unfortunately only the urinary sample was sent to our laboratory and it wasn’t possible to assess serum osmolarity.

The volume status was also not available, which is one of the necessities to adequately interpret hyponatremia OR hypernatremia.

Take Home Message

Salt never goes without water – similarly Sodium shouldn’t be interpreted without the volume status of the patient, and the serum (or urine if applicable) osmolarity.

In hyponatremia one expects the kidneys to respond adequately and hold back sodium, hence decreasing urinary sodium (to <20 mmol/L).

Assuming the patient’s osmolarity was low (by estimation formula) the following possibilities ensue:

Patient Hypervolemic: the high urine sodium points toward renal failure.

Patient Hypovolemic: Renal loss (diuretics / mineralocorticoid deficiency)

Patient Euvolemic: Urine osmolarity should be measured:

Urine Osmol >100: SIADH; Hypothyroidism; Hypoadrenalism (although urine Na usually >30); Stress ; Drug use.

Urine Osmol <100: Primary polydipsia / Beer Potomania syndrome

Variable urinary osmolarity: Needs a “reset” of the osmostat by fluid restriction.

Furthermore: Indicators of renal insufficiency in this patient is the increased creatinine above the patient’s baseline of 48 uM. The creatinine has risen to 88 uM on one occasion. Although not above the reference interval for women, this value constitutes a (88-48)/48 = 83% increase in the creatinine and likely will indicate Acute Kidney injury, probably one of the most overlooked causes of morbidity in hospitalised patients in my opinion.

According to the only source I could find during a quick literature search, I came upon the phrase:

Considering the above, I endeavoured on the task of calculating the half life of the HCG between the 4 time points using Prof Pillay’s method:

F=0.5^(t/T), where F=fraction left, t=time difference and T=half life (units to be kept constant for t and T).

An important log-transformation rule to remember in this case is the logarithm power rule:

Thus to calculate the half life between two time points (after rearranging formula above):

T= (t * log(0.5)) / log(F)

Hence

Between days 0 and 2.5:

T = (2.5 * log(0.5))/ log(203 195/ 1 319 797)

• T (or half life) = 0.92 days

Similarly between days:

• 2.5 and 3.5: T= 0.76 days
• 3.5 and 6.15: T = 1.39 days

This corresponds fairly to the quoted 0.63 days which increases on subsequent days after abortion.

The discrepancy could likely be explained due to:

• some degree of high dose hook effect at the high HCG concentrations,
• high coefficient of variation at high immunoassay analyte concentrations with assays using a sigmoidal calibration curve,
• variation in the methods of abortion compared to or
• gestational age upon which abortion is done, to name a few.

Nonetheless the above equation from Prof Tahir Pillay is useful to calculate half life.

It is important to screen for hyperthyroidism in patients with hydatid moles and ensure that the TFT’s return to normal when the HCG returns to normal.

Abnormal Result

Albumin = 2 g/L

Previous Albumin results: 5 g/L; 11 g/L; 8 g/L all 3 months apart respectively.

Presenting Complaint

The patient did not present with any complaints and the bloods taken was for follow-up only.

History

Patient is known with HIV, diagnosed in 2019 with a CD4 count of 250 cells/uL at the time.

ANA, ANCA, Hepatitis B negative

C3 & C4 normal

The patient presented previously with a left renal vein thrombosis, kidney sizes 150mm and 149mm respectively.

Examination

Not available.

Laboratory Investigations

Current CD4 count= 140 cells/uL.

Urine protein:creatinine ratio of 0.42 (multiple previous values of >1.5 though)

Total Cholesterol 4.2 mmol/L

Other Investigations

Histology

MACROSCOPY:
Specimen consists of a single pale core measuring 6mm in length.

MICROSCOPY:
Glomeruli:
There are a total of 9 glomeruli present. There are no globally sclerosed glomeruli and there are no crescents present. Focal segmental lesions are present. Neutrophils are frequently identified within capillary loops (endocapillary hypercellularity). There is mild focal segmental increase in mesangial cellularity. Glomerular basement membranes appear mildly increased in thickness in areas. There are no features of collapsing FSGS. Podocytes appear prominent. Focal areas suspicious for early spike formation are noted on Jones silver stain.

Tubules:
Tubules show protein resorption droplets with focal areas of ATI. Areas of tubular atrophy and thyroidisation are present. Tubular microcysts are not a feature.

Interstitium:
Moderate lymphoplasmacytic inflammation is present.

Vessels:
Vessels appear normal.

IMMUNOHISTOCHEMISTRY:
IgA: Negative
IgG: membrane staining presnet
IgM: membrane staining present
C3: Negative
C4d: Negative
C1q: 3+ staining present, membrane and mesangial

ELECTRON MICROSCOPY:
Pending – specimen will be processed ex-wax.

PATHOLOGICAL DIAGNOSIS:
Kidney, biopsy:

• Immune complex glomerulonephritis with features suggestive of early membranous nephropathy. DDx=HIVICK. TEM pending.
• Additional acute endocapillary hypercellularity (neutrophils).
• Moderate chronic interstitial inflammation.

Electron microscopy

Ultra-thin resin sections show the presence of electron dense deposits with subepithelial and intramembranous location in keeping with membranous nephropathy.

Ehrenreich-Churg stage: 1-2

Immunohistochemistry:
IgG4: negative.

PATHOLOGICAL DIAGNOSIS:

• Features in keeping with membranous nephropathy.

Final Diagnosis

Membranous Nephropathy

Take Home Message

Severe hypoalbuminemia can occur in nephrotic syndrome. One should ascertain before authorizing such a severely deranged result, that it is not due to a sample type swop of kinds. The history of previously low albumin results was in this case confirmatory. The other features of nephrotic syndrome should also be sought, which is hypertriglyceridemia (no triglyceride value was available in this patient but the Total cholesterol was 4.2 mmol/L).

HIVICK (HIV immune complex disease of the kidney) continues to be an important cause of nephropathy in HIV-naive patients in South Africa. In contrast to HIVAN where the HIV infects the podocytes primarily, HIVICK boasts itself in the fact that it indirectly causes disease by initiating an immune response.

This approach utilizes a completely different offensive strategy that eliminates the need to directly infect the kidney one cell at a time as is the case in HIVAN.

HIVICK is an immune complex attack on the kidney that leads to a variety of histopathologic glomerular lesions: membranous, diffuse/membranoproliferative, IgA nephropathy. The unique aspect of these immune complexes is their composition involving specific HIV antigens as the source target of the antibody response. Therefore the development of HIVICK is completely dependent on the presence of active HIV viremia.

This is a very interesting read on the two diseases: https://www.medscape.com/viewarticle/840389_3

Abnormal Result

Caeruloplasmin 63 mg/dL (15-37 mg/dL)

Presenting Complaint

Not known. Unfortunately no clinical information is known and only a single result is available.

Final Diagnosis

Probably a benign raised caeruloplasmin

Take Home Message

This case, sent through by Dr. John Stanfliet (Pathcare) prompted thorough read-up on caeruloplasmin:

What is the function of caeruloplasmin?

Caeruloplasmin is an alpha-2 glycoprotein that stores and transports copper in the blood. It is produced primarily by the liver. It is to copper what ferritin is to iron. The primary physiological role of caeruloplasmin, however, is acting as a catalyst for reduction and oxidation (redox) reactions.

How is it measured?

Caeruloplasmin is usually measured by immunoturbidimetry or immunonephelometry.

Other methods employed are: oxidation of o-dianisidine (ODA) or that of the traditional reductant, p-phenylenediamine (PPD).

What causes a low caeruloplasmin?

Primary deficiency is rare.

Secondary deficiency is more common and causes include 

(1) dietary copper insufficiency (including malabsorption),

(2) inability to transport Cu2+ from the GI epithelium into the circulation (as in Menkes disease), or

(3) defective incorporation of Cu2+ into the developing caeruloplasmin molecule (as in Wilson disease)

What are causes of an elevated caeruloplasmin?

Concentrations are increased significantly by estrogens (e.g. pregnancy or with the use of oral contraceptives).

It is also a positive acute phase protein thus increased in inflammation. High levels can be seen in active liver disease and in young children where levels can be 50% higher.

High levels is apparently also present in those with lymphoma and rheumatoid arthritis.

Other interesting facts

The normal levels of ceruloplasmin in serum are more or less 10x lower than that of transferrin in molar and mass units.

From other results it is also evident that:

Uric acid nephropathy with hypercalcaemia (Mrs. Linda Meyer) MRN78959694

Abnormal Result

The calcium on 20/02/2019 on bloods taken 14h45 was 3.29 (2.15-2.50 mmol/L).

Presenting Complaint

The patient presented with pain “from loin to groin” which is the typical presentation of passing a renal stone.

History

The patient has chronic renal failure (first creatinine was 362 umol/L with eGFR of 12ml/min – MDRD) on 12 December 2017. Creatinines relatively unchanged since then.

Upon re-evaluation of the case in 2020 it was seen that the baseline creatinine has risen to ~445 umol/L indicating a worsening of the chronic renal failure eGFR now 9 ml/min – by both CKD-EPI and MDRD formulas.

Examination

N/A

Laboratory Investigations

The patient is known with Hyperuricemia, first result 0.50 (0.16-0.36mmol/L) on 16 February 2018.  The response to treatment appears poor due to continuing rising serum uric acid levels (considering whether the patient is on allopurinol).

2. Regarding the hypercalcemia:

From above results a consistent hypercalcemia with a single raised PTH result can be seen – see “Final Diagnosis” and “Take Home Message” below.

Other Investigations

Uric acid crystals were seen on the urine microscopy reflecting uric acid nephropathy – a possible cause of the chronic renal failure, but I could not find any biopsy result or alternative explanation for the renal failure and assume it is uric acid nephropathy.  The patient also appears to have been for a procedure at Urology (? Renal stone removal).

A serum protein electrophoresis with immunofixation (13/09/2018) showed no monoclonal peaks.

Final Diagnosis

Uric acid nephropathy with renal stones.

Hypercalcemia likely due to tertiary hyperparathyroidism.

Take Home Message

Uric acid nephropathy appears to be an uncommon cause of chronic kidney disease (ref. Up-to-date).

It should however be emphesized that clinicians consider the cause on a differential, as it is a manageable cause.

Hypercalcemia sometimes occur in Chronic Kidney Disease patients due to tertiary hyperparathyroidism. This is due to persistent hyperphosphatemia with resulting hyperparathyroidism leading to hypercalcemia (as opposed to the more commonly occuring hypocalcemia is renal failure).

——Commentary by Nephrologist- Dr. Erika Jones——

WRT the Uric Acid

Difficult to say if it is cause or effect of CKD. We can only really make a diagnosis of uric acid nephropathy on kidney biopsy. But it is definitely a cause that we see on occasion.

The good news is that the creatinine has remained fairly stable in the last couple of years, unlike the UA, but as kidney function deteriorates it is expected the UA will increase.

According to our buff records she had staghorn calculi and that was labelled as the cause of her CKD.

Allopurinol in CKD is challenging as it accumulates with side effects. We have had two patients with full on Steven’s Johnson Syndrome. So if she isn’t symptomatic I wouldn’t give it to her. She is recorded as having Sarcoidosis which explains the hypercalcaemia. I think this stage is too early to have tertiary hyperparathyroidism.