Laughing spells and precocious puberty in a child

HOSP # Faku, A RXH 155717598 WARD Endocrine clinic
CONSULTANT   Jody Rusch / Amith Ramcharan DOB/AGE 5y female

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.

Figure 1 – Cellular and molecular mechanisms contributing to GnRH release by normal human hypothalamus. Pulsatile release of GnRH from the GnRH neurons (purple) located in the medial basal hypothalamus is the final common pathway. Excitatory (glutamatergic) and inhibitory (GABAergic) neurons project directly onto the GnRH neuron. At least a subset of GnRH neurons demonstrates paradoxical excitation with GABA input, which is also observed in large HH neurons. Glia-generated influences are also present, with excitation mediated by transforming growth factor α (TGFα) and downstream factors. Kisspeptin-expressing neurons also project directly onto GnRH neurons. HH tissue is universally positive for TGFα but negative for kisspeptin expression. The exact molecular mechanisms responsible for premature pulsatile release of GnRH in association with HH are not understood, but ectopic release from the HH lesion is a viable hypothesis. (From Lomniczi A, Matagne V, Ojeda SR. Neuroendocrinology of puberty. In: Squire LR (Ed). Encyclopedia of Neuroscience. Elsevier, London, 2009. Used with permission.) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533614/