There is a scarcity of literature relating to post-bariatric hypoglycaemia (PBH) in pregnancy. Recurrent hyperglycaemia and hypoglycaemia can have significant consequences for both the mother and the developing fetus. We describe a case of a young pregnant woman who was diagnosed with symptomatic PBH in the second trimester of pregnancy using continuous glucose monitoring (CGM) 3 years after Roux-en-Y gastric bypass (RYGB) surgery. Instigating a low glycaemic index and complex carbohydrate diet significantly improved the patient’s glycaemic excursions. Given that this condition is likely underdiagnosed as a complication of RYGB surgery, a greater awareness of this complication is needed. Patients should be adequately consented pre-operatively for this relatively frequent late surgical complication to enable patients to identify symptoms of this condition at an early stage and seek medical treatment.
PBH is an important diagnosis in patients post-RYGB surgery, particularly in women of childbearing age when consequences of both hyperglycaemia and hypoglycaemia during pregnancy can adversely affect both mother and the fetus.
Adverse outcomes of recurrent hypoglycaemia to the fetus can include small for gestational age, intrauterine growth restriction and possible impairment of beta cell function.
Providing adequate carbohydrate intake to allow growth of the fetus during pregnancy while also attempting to resolve both hyperglycaemia and hypoglycaemia associated with PBH by reducing the intake of simple carbohydrates and high glycaemic index foods can prove challenging.
Patients should be adequately consented for late complications of RYGB surgery such as PBH in order to allow early recognition of symptoms and enable prompt treatment.
NSD1 deletions are associated with the Sotos syndrome, a syndrome of overgrowth in childhood without evidence of endocrine disturbance. Duplications involving the NSD1 gene have been reported to be associated with a ‘reverse Sotos syndrome’ phenotype, characterised by short stature, microcephaly, dysmorphic features and developmental delay. A 2-year-old girl with short stature, dysmorphic features and developmental delay was found to have duplication of 5q32.2–5q32.3, which includes the NSD1 gene. Growth hormone stimulation testing was normal. Growth hormone therapy was initiated at 5 years of age due to severe short stature and growth failure, with height 3.35 standard deviations (SDS) below the median. Growth velocity increased markedly, by +4.91 SDS in the first year of treatment. At the time of last follow-up at 9 years and 11 months, she had achieved a height within 1 SDS of the median. This is the first report of growth hormone therapy for the short stature associated with duplication of the NSD1 gene, showing that despite normal pituitary function, exogenous growth hormone can dramatically improve linear growth.
Sotos syndrome is a disorder of childhood overgrowth caused by NSD1 deletions.
Duplications involving NSD1 cause a ‘reverse Sotos syndrome’ phenotype characterised by short stature and microcephaly.
The contrasting phenotypes of NSD1 deletions and duplications suggest a dose effect.
Stimulated growth hormone secretion is normal in children with NSD1 deletions and duplications.
Growth hormone therapy can be very effective in children with NSD1 duplications, comparable to the response seen in severe growth hormone deficiency.
Polyglandular autoimmune syndrome type II is a rare condition defined by the presence of autoimmune primary adrenal insufficiency along with autoimmune thyroid disease and/or type-I diabetes. Onset of these conditions will usually be separated by several years, though in rare instances it can occur simultaneously. This syndrome can also be associated with various non-endocrine autoimmune diseases, such as vitiligo and alopecia. Coeliac disease is less commonly associated with polyglandular autoimmune syndrome type II and is more commonly associated with polyglandular autoimmune syndrome type III. Here we describe an interesting case of a young male presenting with simultaneous manifestation of Addison’s disease and Graves, with coincident asymptomatic coeliac disease, as a rare manifestation of polyglandular autoimmune syndrome type II.
Polyglandular autoimmune syndrome type II is rare, has female predominance, and peak onset in the third and fourth decades of life.
Onset of Addison’s disease will usually precede or follow onset of type-I diabetes or autoimmune thyroid disease by several years in this syndrome.
Simultaneous onset can occur, as in this case.
Coeliac disease is uncommonly associated with this syndrome.
Coeliac disease is more commonly associated with polyglandular autoimmune syndrome type III.
Coeliac disease should be screened for in patients with associated autoimmune conditions, such as type-I diabetes or autoimmune thyroid disease.
Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome.
Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels.
The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects.
Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.
Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.
Adrenocortical carcinoma is an important differential diagnosis for virilization in young children
Mitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosis
Mitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.
Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completed
In our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.
An adolescent with type 1 diabetes and a history of self-harm, which included intentional overdoses and insulin omission, presented with an insulin degludec overdose. She had been commenced on the ultra-long-acting insulin, degludec, with the aim of reducing ketoacidosis episodes in response to intermittent refusal to take insulin. Insulin degludec was administered under supervision as an outpatient. Because it was anticipated that she would attempt a degludec overdose at some stage, the attending clinicians implemented a proactive management plan for this (and related) scenarios. This included long-term monitoring of interstitial glucose using the Abbott Freestyle Libre flash glucose monitor. The patient took a witnessed overdose of 242 units of degludec (usual daily dose, 32 units). She was hospitalised an hour later. Inpatient treatment was guided primarily by interstitial glucose results, with capillary and venous glucose tests used as secondary measures to assess the accuracy of interstitial glucose values. Four days of inpatient treatment was required. The patient was managed with high glycaemic loads of food and also intermittent intravenous dextrose. No hypoglycaemia was documented during the admission. In summary, while a degludec overdose may require several days of inpatient management, in situations where proactive management is an option and the dose administered is relatively modest, it may be possible to avoid significant hypoglycaemia. In addition, this case demonstrates that inpatient interstitial glucose monitoring may have a role in managing insulin overdose, especially in situations where the effect of the insulin overdose on glucose levels is likely to be prolonged.
Degludec overdoses have a prolonged effect on blood glucose levels, but if the clinical situation allows for early detection and management, treatment may prove easier than that which is typically needed following overdoses of a similar dose of shorter acting insulins.
Inpatient real-time interstitial monitoring helped guide management, which in this context included the prescription of high dietary carbohydrate intake (patient led) and intravenous 10% dextrose (nurse led).
Use of inpatient interstitial glucose monitoring to guide therapy might be considered ‘off label’ use, thus, both staff and also patients should be aware of the limitations, as well as the benefits, of interstitial monitoring systems.
The Libre flash glucose monitor provided nurses with low cost, easy-to-use interstitial glucose results, but it is nevertheless advisable to check these results against conventional glucose tests, for example, capillary ‘finger-stick’ or venous glucose tests.
B J WheelerPaediatric Endocrinology, Southern District Health Board, Dunedin, New Zealand Department of Women’s and Children’s Health, University of Otago, Dunedin School of Medicine, Dunedin, New Zealand
In clinical practice, seizures independent of hypoglycemia are observed in patients with type 1 diabetes mellitus (T1DM) more frequently than expected by chance, suggesting a link. However, seizures during management of diabetic ketoacidosis (DKA) have generally been considered a bad prognostic factor, and usually associated with well-known biochemical or neurological complications. We present the case of a 17-year-old girl with known T1DM managed for severe DKA complicated by hypocapnic seizure. We review the literature on this rare occurrence as well as outline other possible differentials to consider when faced with the alarming combination of DKA and seizure.
Seizures during DKA treatment require immediate management as well as evaluation to determine their underlying cause.
Their etiology is varied, but a lowered seizure threshold, electrolyte disturbances and serious neurological complications of DKA such as cerebral edema must all be considered.
Sudden severe hypocapnia may represent a rare contributor to seizure during the treatment of DKA.
Benjamin J WheelerDepartment of Women's and Children's Health, University of Otago, Dunedin School of Medicine, PO Box 56, Dunedin 9054, New Zealand Paediatric Endocrinology, Southern District Health Board, Dunedin, New Zealand
Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.
Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.
The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.
As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.
Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.