Samson O Oyibo, Olivia S Green, Nabeel M Laliwala, and Satyanarayana V Sagi
Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan’s syndrome and postpartum autoimmune hypophysitis or due to a primary thyroid disease as in postpartum thyroiditis. It is important that the correct diagnosis is ascertained because hypothalamic or pituitary disorders are often associated with other pituitary hormone deficiencies, especially life-threatening adrenal insufficiency or adrenal crisis. A combination of various symptoms and biochemical markers, especially serum thyroid-stimulating hormone levels dictate the initial diagnostic pathway. We present a case of a woman who presented with a 2-month history of tiredness and neck discomfort following delivery. A thyroid function test demonstrated results, which we initially interpreted as central hypothyroidism. Follow-up results indicated that this was in fact the transition period between the thyrotoxic phase and hypothyroid phases of postpartum thyroiditis. This case highlights the potential for diagnostic confusion between central hypothyroidism and postpartum thyroiditis.
- Postpartum thyroiditis affects one in twenty mothers within 12 months of delivery.
- The majority of patients have transient thyrotoxicosis only, some have transient hypothyroidism only, and the rest has a triphasic pattern (thyrotoxic, hypothyroid then a euthyroid phase).
- During the transition from the thyrotoxic phase to hypothyroid phase, when serum TSH is still suppressed, the biochemical results can resemble that of central hypothyroidism.
- If central hypothyroidism is suspected, then urgent diagnostic investigations should be carried out along with the assessment of adrenal function.
- There is a potential for diagnostic confusion between postpartum central hypothyroidism and postpartum thyroiditis; however, the obstetric history, clinical symptoms, and signs (headaches, breastfeeding, goitre, etc.) and serum adrenocorticotropic levels should help with the differential diagnosis.
Satyanarayana V Sagi, Hareesh Joshi, Jamie Trotman, Terence Elsey, Ashwini Swamy, Jeyanthy Rajkanna, Nazir A Bhat, Firas J S Haddadin, Samson O Oyibo, and Soo-Mi Park
Familial hypocalciuric hypercalcaemia (FHH) is a dominantly inherited, lifelong benign disorder characterised by asymptomatic hypercalcaemia, relative hypocalciuria and variable parathyroid hormone levels. It is caused by loss-of-function pathogenic variants in the calcium-sensing receptor (CASR) gene. Primary hyperparathyroidism (PHPT) is characterised by variable hypercalcaemia in the context of non-suppressed parathyroid hormone levels. Unlike patients with FHH, patients with severe hypercalcaemia due to PHPT are usually symptomatic and are at risk of end-organ damage affecting the kidneys, bone, heart, gastrointestinal system and CNS. Surgical resection of the offending parathyroid gland(s) is the treatment of choice for PHPT, while dietary adjustment and reassurance is the mainstay of management for patients with FHH. The occurrence of both FHH and primary hyperparathyroidism (PHPT) in the same patient has been described. We report an interesting case of FHH due to a novel CASR variant confirmed in a mother and her two daughters and the possible coexistence of FHH and PHPT in the mother, highlighting the challenges involved in diagnosis and management.
- Familial hypocalciuric hypercalcaemia (FHH) and primary hyperparathyroidism (PHPT) can coexist in the same patient.
- Urinary calcium creatinine clearance ratio can play a role in distinguishing between PHPT and FHH.
- Genetic testing should be considered in managing patients with PHPT and FHH where the benefit may extend to the wider family.
- Family segregation studies can play an important role in the reclassification of variants of uncertain significance.
- Parathyroidectomy has no benefit in patients with FHH and therefore, it is important to exclude FHH prior to considering surgery.
- For patients with coexisting FHH and PHPT, parathyroidectomy will reduce the risk of complications from the severe hypercalcaemia associated with PHPT.
Satyanarayana V Sagi, Hareesh Joshi, Emily Whiles, Mondy Hikmat, Vijith R Puthi, Jane MacDougall, Sarah L Spiden, Gavin Fuller, Soo-Mi Park, and Samson O Oyibo
Hypogonadotropic hypogonadism is characterised by insufficient secretion of pituitary gonadotropins resulting in delayed puberty, anovulation and azoospermia. When hypogonadotropic hypogonadism occurs in the absence of structural or functional lesions of the hypothalamic or pituitary gland, the hypogonadism is defined as idiopathic hypogonadotropic hypogonadism (IHH). This is a rare genetic disorder caused by a defect in the secretion of gonadotropin releasing hormone (GNRH) by the hypothalamus or a defect in the action of GNRH on the pituitary gland. Up to 50% of IHH cases have identifiable pathogenic variants in the currently known genes. Pathogenic variants in the GNRHR gene encoding the GNRH receptor are a relatively common cause of normosmic IHH, but reports of pathogenic variants in GNRH1 encoding GNRH are exceedingly rare. We present a case of two siblings born to consanguineous parents who were found to have normosmic idiopathic hypogonadotropic hypogonadism due to homozygosity of a novel loss-of function variant in GNRH1. Case 1 is a male who presented at the age of 17 years with delayed puberty and under-virilised genitalia. Case 2 is a female who presented at the age of 16 years with delayed puberty and primary amenorrhea.
- IHH is a genetically heterogeneous disorder which can be caused by pathogenic variants affecting proteins involved in the pulsatile gonadotropin-releasing hormone release, action, or both.
- Currently known genetic defects account for up to 50% of all IHH cases.
GNRH1 pathogenic variants are a rare cause of normosmic IHH.
- IHH is associated with a wide spectrum of clinical manifestations.
- IHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty.
- Early diagnosis and gonadotrophin therapy can prevent negative physical sequelae and mitigate psychological distress with the restoration of puberty and fertility in affected individuals.