Summary

Pituitary adenomas are intracranial neoplasms, usually demonstrating a benign phenotype. We present the case of 21-year-old male with an 18-month history of reduced visual function (acuity and field) in the left eye. Based on neuroimaging and endocrine profile, a giant prolactinoma causing hypogonadotropic hypogonadism was diagnosed and cabergoline was commenced. After a month of treatment, the tumour size reduced, and visual function improved to normal; however, he developed Foster Kennedy syndrome with a swollen right optic disc. After almost 1 year of follow-up, he regained full visual functioning. Two years since his diagnosis, his prolactin remains normal with no adverse effects or further visual complications.

Learning points

• Foster Kennedy syndrome is a rare entity but can be a feature of pituitary adenomas.

• Visual deterioration secondary to a compressive optic neuropathy can be reversible, provided that diagnosis and treatment are prompt.

• This case highlights the importance of frequent monitoring of visual function during follow-up of these lesions, particularly when there are deficits at diagnosis.

Summary

A 37-year-old female of South Asian origin was referred to our diabetes clinic for evaluation of an unusual finding during her retinal screening. Her retinal blood vessels appeared white in contrast to the normal pink-red colour. She had type I hyperlipidaemia, confirmed by genotype, and was recently diagnosed with diabetes, secondary to pancreatic insufficiency, for which she had suboptimal control and multiple hospitalisations with recurrent pancreatitis. On examination, she had multiple naevi on her skin; the rest of the examination was unremarkable. The patient did not report any visual disturbances and had intact visual acuity. Investigations showed raised total cholesterol (12.5 mmol/L) and triglycerides (57.7 mmol/L). Following evaluation, the patient was diagnosed with lipaemia retinalis, secondary to type I hyperlipidaemia. The patient was managed conservatively to reduce the cholesterol and triglyceride burdens. However, therapies with orlistat, statin, fibrates and cholestyramine failed. Only a prudent diet, omega-3 fish oil, medium-chain triglycerides oil and glycaemic control optimised with insulin showed some improvements in her lipid profile. Unfortunately, this led her to becoming fat-soluble vitamin deficient; hence, she was treated with appropriate supplementation. She was also recently started on treatment with volanesorsen. Following this, her lipid parameters improved and lipaemia retinalis resolved.

Learning points

• Lipaemia retinalis is an uncommon incidental finding of type I hyperlipidaemia that may not affect vision.

• Management of associated dyslipidaemia is challenging with minimal response to conventional treatment.

• Increased awareness of lipaemia retinalis and specialist management is needed as part of regular patient monitoring and personalised management.

Summary

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.

Learning points

• 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.

Summary

Tyrosinaemia type 1 (TT1) is a rare inherited disorder of amino acid metabolism typically presenting with liver failure and renal tubular dysfunction. We describe three individuals with TT1 and transient hyperinsulinaemic hypoglycaemia (HH). Two siblings with TT1 and acute liver dysfunction were diagnosed with hyperinsulinaemic hypoglycaemia in the neonatal period. Both siblings were successfully treated with diazoxide/chlorthiazide and treatment was gradually weaned and stopped after 8 and 6 months of age respectively. The third patient presented with a neonatal liver failure with mild cholestasis, coagulopathy, fundus haemorrhages, vitamin A and E deficiency and hyperinsulinaemic hypoglycaemia. He maintained euglycaemia on high dose diazoxide (5–12 mg/kg/day) but developed pulmonary hypertension at 12 weeks of age. After discontinuation of diazoxide, he continued maintaining his blood glucose (BG) within the normal range. Although histological abnormalities of the pancreas including beta-cell hyperplasia are well documented, the exact mechanism of excessive insulin secretion in TT1 is not well understood. It may be related to the accumulation of toxic metabolites in the target organs including pancreas. Therefore, in patients with TT1 and persistent hypoglycaemia beyond the recovery of the acute liver failure, it is important to exclude hyperinsulinism which is usually transient and can be successfully treated with diazoxide and chlorothiazide. Further studies are required to determine which factors contribute to excessive insulin secretion in patients with TT1.

Learning points:

• Every child with TT1 should be monitored for signs and symptoms of hypoglycaemia and screened for HH at the time of real hypoglycaemia.

• If hypoglycaemic episodes persist even after improvement of liver function, hyperinsulinism should be suspected.

• Treatment with diazoxide is effective, however, children need to be monitored closely for possible side effects.

• The pathophysiological mechanism of hyperinsulinism in children with TT1 is not elucidated yet and further studies are required to determine which factors contribute to excessive insulin secretion in patients with TT1.

Summary

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.

Learning points:

• 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.

Summary

Diabetic myonecrosis, also known as diabetic muscle infarction is a rare complication of diabetes mellitus usually associated with longstanding suboptimal glycaemic control. Although theories of atherosclerosis, diabetic microangiopathy, vasculitis, ischaemia-reperfusion injury and hypercoagulable state have been proposed to explain the pathophysiology, none of these have been able to individually explain the pathophysiology in entirety. Diabetic renal disease is the most common risk factor for developing DMN and its recurrence. The diagnosis is often missed due to lack of awareness and the presentation mimicking other conditions associated with DM. The routine laboratory investigations are often non-specific and do not provide much value in the diagnosis as well. Muscle biopsy can provide a definite diagnosis but is not currently recommended due to its invasiveness and association with prolonged time to symptoms resolution. Magnetic resonance imaging, in combination with classic history and risk factors can clinch the diagnosis. Treatment is generally analgesia and rest, although the former’s use may be limited in the presence of renal disease.

Learning points:

• Diabetic myonecrosis is a rare complication of diabetes mellitus associated with longstanding suboptimal glycaemic control.

• Diabetic renal disease is a known risk factor, although the evidence is merely observational.

• Although muscle biopsy could provide a definite diagnosis, it is not recommended as it can prolong the disease process and should be reserved only for cases not responding to conventional treatment.

• Typical MRI findings in combination with classic symptoms and risk factors can clinch the diagnosis

• Current treatment recommendations include NSAIDs and/or aspirin (if not contraindicated) alongside bed rest. Physiotherapy is not recommended in the acute phase but should be started as soon as patient is discharged from hospital.

• Optimal glycaemic control is key to prevent recurrence.

Learning points:

• CVC insertion is one of the most significant risk factors for thrombosis in the paediatric population.

• Risk factors for CVC-associated thrombosis include increased duration of CVC placement, malpositioning and infusion of blood products.

• To our knowledge, this is the first study to evaluate CVC-associated thrombosis in patients with congenital hyperinsulinism (CHI).

• The incidence of CVC-associated thrombosis development is significant (18%) in CHI patients and higher compared to other neonates with CVC. CHI severity may be a risk factor for thrombosis development.

• Although effective prophylaxis for CVC-associated thrombosis in infancy is yet to be established, our preliminary experience suggests the safety and efficacy of enoxoaparin prophylaxis in this population and requires on-going evaluation.

Learning points:

• Hirsutism in postmenopausal women should trigger suspicion of androgen-secreting tumor

• Extremely elevated testosterone level plus normal DHEAS level point toward ovarian source

• Leydig cell tumor is extremely rare cause of hyperandrogenicity

Learning points

• Hyperandrogenism in pregnancy is rare.

• Clinical features are similar to the non-pregnant state in the mother but virilisation in the foetus can have profound consequences.

• HL and pregnancy luteoma are the most common ovarian pathologies leading to hyperandrogenism in pregnancy.

• Spontaneous regression occurs in the post-partum period in the vast majority of cases and surgery is only required for local complications.

Learning points

• Patients with type 1 PHA are likely to present in the neonatal period with hyponatraemia, hyperkalaemia and metabolic acidosis and can be diagnosed by the significantly elevated plasma renin activity and aldosterone levels.

• The differential diagnosis of type 1 PHA includes adrenal disorders such as adrenal hypoplasia and congenital adrenal hyperplasia; thus, adrenal function including cortisol levels, 17-hydroxyprogesterone and a urinary steroid profile are required. Secondary (transient) causes of PHA may be due to urinary tract infections or renal anomalies; thus, urine culture and renal ultrasound scan are required respectively.

• A differentiation between renal and systemic PHA type 1 may be made based on sodium requirements, ease of management of electrolyte imbalance, sweat test results and genetic testing.

• Management of renal PHA type 1 is with sodium supplementation, and requirements often decrease with age.

• Systemic PHA type 1 requires aggressive and intensive fluid and electrolyte management. Securing an enteral feeding route and i.v. access are essential to facilitate ongoing therapy.

• In this area of the UK, the incidence of AD PHA and AR PHA was calculated to be 1:66 000 and 1:166 000 respectively.