Abnormal Result

Thyroglobulin value of <0.1 ug/L upon signing results out.

Presenting Complaint

Patient presented with a neck “swelling” in October 2016. Systemic complaints were not inquired, but none was reported.

History

TFT: euthyroid since presentation when the thyroid functions were first tested in 2016.

Examination

A solitary thyroid nodule was found in the neck, moving with swallowing.

Laboratory Investigations

TFT: euthyroid upon presentation, which is clear from the table below.

From results above it can be seen that the patient was euthyroid upon presentation (in 2016 and later until excision – highlighted in bold)

Hemithyroidectomy was done in May 2018, and another hemithyroidectomy in September 2018, thus the thyroglobulin after the first and second surgery was still detectable, but absent after September 2018.

Other Investigations

Ultrasound upon first presentation was indicative of a “suspicious nodule” in the thyroid gland.

Final Diagnosis

PATHOLOGICAL DIAGNOSIS – excision biopsy of nodule (17/01/2018)

Specimen A:
Right lobe of thyroid, hemithryoidectomy:
Encapsulated follicular variant of papillary thyroid carcinoma
Specimen B:
Right cervical lymph node (Level VI), biopsy:
Negative for malignancy (0/1)

PATHOLOGICAL DIAGNOSIS – left thyroid lobectomy (11/05/2018):

Left lobe of thyroid, excision: Negative for malignancy

PATHOLOGICAL DIAGNOSIS:

Right thyroid, lobectomy: Negative for malignancy (05/09/2018):

Take Home Messages

• Thyroglobulin level is directly proportional to thyroid tissue present in vivo, hence is a useful tumour marker for thyroid cancer.
• Anti-thyroglobulin antibody level is tested with Thyroglobulin to exclude false low values of thyroglobulin. If Anti-thyroglobulin Ab levels are increased with a decreased thyroglobulin level, the decrease in tumour marker is likely due to immunological clearance of the thyroglobulin and the result is hence likely false. This is the reason for the following canned text in TrakCare when the thyroglobulin level measures low:

The presence of thyroglobulin antibodies may interfere with the
thyroglobulin assay. The result of this test must be treated with reserve
if the patient has a positive thyroglobulin antibody test.

TrakCare canned text for low thyroglobulin

• Upon total removal of the thyroid, thyroid replacement therapy is necessary, preferably slightly hyperthyroid levels to suppress TSH, and hence prevent tumour growth, as is also evidenced by this patient’s TSH and free T4 results.
• As with most other tumour markers, thyroglobulin should be used for follow-up as a proxy of tumour size or regression.

Abnormal Result

Aldosterone: 1380 pmol/L

Renin: 2.1 ng/L

Aldosterone: Renin ratio: 657.14 pmol/ng

Presenting Complaint

Uncontrolled Hypertension, unresolved on maximum dose of 3 antihypertensives.

History

Examination

Laboratory Investigations

Other Investigations

Urine electrolytes

Serum Results

Urine metanephrines

Final Diagnosis

Primary hyperaldosteronism causing secondary hypertension with accompanying renal injury.

Take Home Messages

Abnormal Result

Urea 0.8 mmol/L; Creatinine 10 umol/L; Sodium 154 mmol/L; Potassium 5.4 mmol/L

Presenting Complaint

Above results do not make sense for a 33 year old female, except if muscle weight is extremely low.

History

Examination

N/A

Laboratory Investigations

Inspection of the sample:

Other Investigations

Lactate on analyser as done on serum sample: >22 mmol/L, dilution made: 1 in 10 revealed a lactate of 26.8 mmol/L in the sample. This could explain that Ringers Lactate was the contaminant in the sample, but can only be hypothesized with the available evidence.

Hematology results:

Final Diagnosis

Take Home Messages

Abnormal Result

Sodium = 198 mmol/L (H) (136-145)

Presenting Complaint

1 day of poor feeding.  Child passing very hard/ dark brown stool for the preceding 10 days.

History

Birth weight @ term: 3.380kg.  Delivered vaginally after induction of labour because of spontaneous rupture of membranes at 40 weeks gestation. Discharged home without any problems after 1 day.

Examination

On arrival at district hospital: Temp: 38^oC, Sats 96% on Nasal O2, Finger prick glucose: 10mmol/L, Capillary refill time: 6 seconds,

HR: 140bpm. 

Blood gas:

pH: 7.26,

BE -16.3,

pCO­₂ 3.2 kPa,

Na 190.

Weight: 2.2kg (birth weight: 3.380 kg, thus 35% weight loss)

Laboratory Investigations

Other Investigations

Urine organic acid analysis by GCMS demonstrates elevation of the liver markers 4-OH-phenyllactate and 4-OH-phenylpyruvate together with lactaturia. Succinylacetone, a marker for tyrosinaemia type 1 is absent. Moderate ketonuria with elevated dicarboxylic acids C6, C8, and C10 is also present, these changes suggest a lipolytic response to catabolic or fasting stress or hypoglycaemia together with underlying hepatic dysfunction with lactataemia but are non-specific for an IMD per se. 

Final Diagnosis

Patient was pure water depleted with a sodium concentration of 198 mmol/L.  The mother was not lactating adequately despite the infant sucking well, evidenced by the fact that when expressed breast milk was tried, there was too little milk for the baby to drink.  The nurses’ notes confirmed this finding.  This finding also confirms the failure to produce stool volume and the normal urine organic acid profile with evidence of starvation / fasting stress.

Take Home Messages

When considering a patient with high plasma sodium concentration it is
important to bear in mind:

1. Hypernatremia does not necessarily indicate an excess of extracellular sodium.  Except in rare cases of salt overload most patient with hypernatremia have a deficiency of both water and sodium, with the water deficiency being proportionally higher than that of sodium.
2. Patients become hypernatremic because the water lost from the body exceed the intake and there is negative fluid balance.  The amount of water which a person can drink generally exceeds by far the amount lost from the body in most pathological fluid-losing disorders, eg. Diarrhoea, sweating.  Patients thus become hypernatremia due to:
   1. Too old, young or sick to drink
   2. Obstruction of oesophagus
   3. Disorders of thirst centre
   4. No access to water                          

Ref: Walmsley – Cases in Chemical Pathology 4^th
ed.

It is also important:

1. To calculate the Osmolar gap( difference between calculated and measured osmolarity)
2. U:P osmol (>1 = hypotonic fluid depletion, pure water loss or salt gain; ~1 = osmotic diuresis; <1 = diabetes insipidus ~the various causes of nephrogenic and neurogenic DI)

Abnormal Result

Prolactin 10 986.0 ug/L (4-15.2) 

Dilutions:

1/10  >4700;

1/100 = 10821;

1/50 = 10 986.

Presenting Complaint

Epistaxis

History

Patient with epistaxis referred to the ENT specialist clinic.  No relevant medication history.

Examination

35 y male with a large left post-nasal space mass, a vascular mass involving the pituitary fossa.

?NBL (non-benign lesion)

?Sinonasal malignancy

?Pituitary Tumour

Laboratory Investigations

TSH 0.91 pmol/L (0.27-4.20)

Free T4 15.7 pmol/L (12-22)

FSH 0.8 IU/L ↓ (1.5-12.4)

LH 0.2 IU/L ↓ (1.7-8.6)

Testosterone 0.2 nmol/L ↓ (8.6-29.0)

PTH 1.7 pmol/L (1.6-6.9)

Prolactin measuring method:

The Elecsys prolactin sandwich immunoassay uses two monoclonal
antibodies directed against human prolactin.

R1 = biotinylated antibody – recognizes the N-terminal end of the
prolactin molecule

R2 – ruthenium complexed antibody probably reacts with a region in the
middle of the prolactin molecule.

1^st incubation: a biotinylated monoclonal prolactin-specific
antibody and a monoclonal prolactin-specific antibody labeled with a ruthenium
complex form a sandwich complex.

2^nd incubation: after addition of streptavidin-coated
microparticles, the complex becomes bound to the solid phase via interaction of
biotin and streptavidin.

Reaction mixture aspirated into the measuring cell where microparticles
are magnetically captured into the surface of the electrode.   Unbound substances are then removed with
ProCell. 

Application of a voltage to the electrode then induces
chemiluminescent emission which is measured by a photomultiplier, results
calculated by a standard curve.

Other Investigations

Monomeric prolactin – 7744 ug/L (70% recovery after PEG precipitation)

Biopsy: confirmed tumour stained strongly positive
with prolactin suggesting a prolactinoma.

Final Diagnosis

Pituitary Macroprolactinoma

Take Home Messages

Sandwich immunoassays are prone to high dose hook-effect. There are
various ways to overcome this effect. (This will later be expanded on – see AFP
/ Beta-HCG).

Prolactin appears in the serum as:

1. Active monomeric
   prolactin (“little”) (80%) 23kDa
2. Inactive dimeric
   prolactin (“big”) (5-20%) 50-60kDa
3. Low activity
   tetrameric prolactin (“big-big”) (0.5-5%) 150-170kDa 

Precipitation by PEG yields the active monomeric
prolactin, expressed as a percentage recovery after precipitation.  Big-big prolactin consists of an
antigen-antibody complex of monomeric prolactin-immunoglobulin G and is defined
as macroprolactin.  This has a long
half-life in blood when compared to normal prolactin and gives false high
readings of prolactin, leading to unnecessary investigations in certain
cases.  A high prolactin should thus be
confirmed by doing a PEG precipitation.

Abnormal Result

Fluid triglycerides were requested on three samples, without any clinical information.

Presenting Complaint

The laboratory history was explored, to find that the patient had three subsequent samplings daily from a pleural fluid cavity.

History

A month prior to presentation, the patient had a breached stillbirth.

The following was found on Histology:

EPISODE NUMBER:
SA03381462
CLINICAL DETAILS:
23 year old female. G02 P2-1. VDRL: negative. Smoking: 8/day. Alcohol: none. HIV: negative. 750g breech stillbirth at 28/40.
MACROSCOPY:
The plate measures 130 x 100 x 30mm and weighs 196.8g.
The membranes are complete without evidence of meconium staining.
The cord measures 300mm in length with an average diameter of 15mm. Three umbilical vessels are identified with 3 twists per 100mm. The cord insertion is off-centre, 20mm from the plate margin.
Congested blood vessels are identified on examination of the foetal surface.
Cut-sections of the plate show:
- Retroplacental clot.
MICROSCOPY:
General:
Placental weight for gestational age is below the 10th percentile at 196.8g. Partial autolysis is present throughout the specimen.
The umbilical cord and membranes:
The umbilical cord contains two arteries and one vein. There is no evidence of vasculitis or funisitis. Wharton's jelly and membranes do not show meconium uptake. The amniocytes are intact and show no evidence of vacuolation or hyperplasia.
Chorionic plate:
The chorionic plate vessels are focally dilated. There is no evidence of chorioamnionitis.
Villi and intervillous spaces:
The stem villous vessels show partial obliteration as well as stromal sclerosis. Distal villous hypoplasia as well as accelerated villous maturation is seen. Intervillous thrombi are seen as well as intraparenchymal extension of the retroplacental haematoma. There is no evidence of infarction, villitis or intervillositis.
Maternal surface:
There is evidence of a large retroplacental haematoma. No chronic deciduitis or untransformed blood vessels are seen.
PATHOLOGICAL DIAGNOSIS:
Placenta, examination:
Maternal vascular malperfusion.
Retroplacental haematoma.
Reported by: Dr M Du Toit

Clinicians were indeed querying a chylothorax. A thoracic duct injury was suspected.

Examination

Unfortunately little clinical information is known, as can be seen above. The following table shows the clinical info which has been captured on the respective episodes’ request forms:

      Clinical history for episodes 
< SA03215505 >      ?UTI IN PREGNANCY
< SA03381462 > 03/10/2019     PLACENTA
< SA03466495 > 07/11/2019     MEDIASTINITIS
< SA03466500 > 08/11/2019     MEDIASTINITIS
< SA03466533 > 08/11/2019     MEDIASTINITIS
< SA03467168 > 08/11/2019     MEDIASTINITIS
< XC00366131 >      ILLEG
< SA03467081 >      ILLEGIBLE
< SA03469305 >      NECK ABSCESS
< SA03469995 >      ILLEGIBLE
< SA03472064 >      MEDIASITINITIS
< SA03470738 >      NECK ABSCESS
< SA03476491 >      PUS FLUID + MEDIASTINITIS
< SA03476496 >      PUS / FLUID + MEDIASTINITIS
< SA03476502 >      PUS / FLUID + MEDIASTINITIS
< SA03476507 >      PUS / FLUID + MEDIASTINITIS
< SA03489396 >      ?CHYLOTHORAX
< SA03485823 >      SEPSIS
< SA03491179 >      NECK ABSCESS
< SA03493180 >      Neck abscess with sepsis.
< SA03494446 >      CVC TIP
< SA03509355 >      LOOSE STOOLS
< SA03513657 >      THORACIC SURGERY
< SA03531013 >      MEDIASTINITIS

Laboratory Investigations

Other Investigations

Final Diagnosis

A pleural fluid triglyceride >1.24 is suggestive of chylothorax.

The additional finding of a thin white layer present on the top of the sample after centrifugation indicates the presence of chylomicrons in the sample, which further supports the diagnosis of chylothorax.

Take Home Messages

The primary role of the thoracic duct is to carry 60 – 70% of ingested fat at a concentration of 0.4 – 6 g/dl from the intestine to the circulatory system.

• Chyle contains large amounts of cholesterol, triglycerides, chylomicrons and fat soluble vitamins.
• Lymph is the other main constituent of chyle and is made up of
  • immunoglobulins
  • enzymes
  • between 400 and 6800 white blood cells/ml, the majority of which are lymphocytes.
• Chyle transportation is maximal after a high fat meal and minimal with starvation where flow is reduced to almost a trickle.

Classically, a chyloma, a collection of chyle below the pleura develops when the thoracic duct first leaks. Although rarely detected, it manifests itself as a swelling in the supraclavicular fossa which may be associated with severe chest pain, dyspnoea and tachycardia.

Chylomas can also manifest themselves at other sites of the pleura without causing supraclavicular swelling. Eventually the chyloma bursts through the pleura where the chyle accumulates in the pleural space.

Very rarely, the chyle leak may lead to chylomediastinum or chylopericardium.

Abnormal Result

21/08/2018 Two ACTH tests (referred to another laboratory) and two
Cortisol levels (at our laboratory) were done. 
At first it was thought to be a dexamethasone suppression test, but then
realized the clinicians were suspecting hypopituitarism.

10h05: ACTH 0.7 pmol/L ↓ (1.6-13.9)  Cortisol  8 nmol/L ↓  (Morning: 133- 537; Afternoon 68 – 327)

10h35: ACTH 1.8 pmol/L N (1.6-13.9) 
Cortisol  68 nmol/L ↓  (Morning: 133- 537; Afternoon 68 – 327)

Presenting Complaint

? hypopituitarism

History

Known with a pituitary macroadenoma, previously seen at the Radiotherapy clinic in 2016.

Examination

No clinical info available.

For Primary adrenal insufficiency one would expect: Hyperpigmentation
(due to ↑ ACTH), +/- hyperkalemia/hyponatremia (aldosterone effect), +/-
virilization.

For Secondary adrenal insufficiency there is subtle symptoms, electrolytes are not deranged significantly because aldosterone function is preserved. See table on Bishop 7^th ed. p. 459.

Laboratory Investigations

Measurement of
plasma ACTH concentration is used to assess Cushing’s disease, adrenal tumors,
ectopic ACTH-producing tumors, Addison’s disease, Nelson’s syndrome, and
hypopituitarism.

The
laboratory diagnosis of hypopituitarism, however is relatively straightforward.
In contrast to the primary failure of an endocrine gland that is accompanied by
dramatic increases in circulating levels of the corresponding pituitary tropic
hormone, secondary failure (hypopituitarism) is associated with low or normal
levels of tropic hormone.  This is the
diagnosis in this case with the history of previous radiotherapy which was
given for a macro-adenoma.

Other Investigations

Free T4 on 19/04/2018 was 7.8 pmol/L (12-22), also suggesting possible hypopituitarism, although a TSH would be helpful.

Final Diagnosis

Hypopituitarism confirmed.

Take Home Messages

Dexamethasone suppression test need only measurement of cortisol, not accompanying ACTH, except in extended work-up however, where a Cosyntropin (CRH) stimulation test can be done to distinguish between pituitary or hypothalamic insufficiency.

Evaluation of pituitary function need the Primary hormone (Cortisol) as well as the tropic hormones from the pituitary (ACTH).

12/08/2018: Na 156 mmol/L (H)         Urea 4.2mmol/L       Tot. Bili 4 umol/L K 1.9 mmol/L (L)             Creat 88 umol/L       ALT 82 U/L Cl 97.9 mmol/L (L)          Gluc 3.52 mmol/L     AST 238 U/L                  Ammonia 35 umol/L Bicarb 16.6 mmol/L (L)    Osmol 310 mmol/L (H)        Osmolar gap: -10 mM    Anion Gap: 47 mmol/L    

Marked elevation of hepatocellular enzymes, ductal enzymes within normal range.  Within the course of three days the patient developed Klebsiella Pneumoniae on intubation in ICU with DIC and marked renal failure (Creat 506, Urea 26.8) and demised in ICU 3 days after admission, although liver enzymes were not markedly more deranged as initial presentation.