Summary

Menstrual cycle abnormalities are common in premenopausal females with Cushing’s syndrome, although the underlying mechanism is poorly understood. Signs and symptoms found in Cushing’s syndrome overlap with polycystic ovarian syndrome (PCOS). The patient is a 33-year-old female previously diagnosed by a gynecologist with PCOS and treated with oral contraceptive pills (OCPs) for 2 years. She then discontinued her OCPs without consulting a clinician, resulting in amenorrhea for 6 months, for which she presented. She also had symptoms of depression and anxiety but had no other signs and symptoms of Cushing’s syndrome, except a plethoric face. Initial lab work showed evidence of central hypogonadism (low luteinizing hormone, follicle-stimulating hormone, and estrogen), so a complete anterior pituitary hormone workup was done. Her thyroid-stimulating hormone was also low with a low free T4 level. Prolactin level was normal, but surprisingly, her AM cortisol level was high. The Cushing’s syndrome workup revealed non-suppressed cortisol after a 1 mg dexamethasone suppression test and positive 24-h urine cortisol with suppressed adrenocorticotrophic hormone. A CT scan of her adrenal glands revealed a left adrenal adenoma. She underwent a left adrenalectomy, after which her menstrual cycles became regular again, and pituitary function has recovered.

Learning points

• In Cushing's syndrome, female patients can have menstrual abnormalities due to the high cortisol levels, which can affect gonadotrophin levels.

• We encourage clinicians to include Cushing's syndrome in the differential diagnosis of patients with central hypogonadism.

Summary

Moyamoya syndrome (MMS) refers to a rare cerebrovascular disorder characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches, leading to an increased risk of stroke. While prevalent in Asia, this condition is considerably less common in Western countries, including Europe. The association between MMS and Graves’ disease (GD) has been well documented, primarily in Asian and American populations, notably Latin Americans. In this report, we report the first case of GD with MMS in a Caucasian woman from Western Europe. The precise mechanisms underpinning the correlation between these two conditions remain poorly elucidated but are hypothesized to involve hemodynamic alterations, the toxic effects of anti-thyroid-stimulating hormone receptor antibodies, or a shared genetic predisposition. Our clinical case underscores the significance of thyroid disease screening in suspected MMS cases, as the management of thyroid dysfunction may suffice to improve neurological symptoms.

Learning points

• The association between Graves’ disease (GD) and Moyamoya syndrome (MMS) can manifest in a Caucasian European patient.

• Screening for thyroid disease is essential when MMS is suspected, as treating GD might effectively alleviate neurological symptoms.

• The mechanisms linking GD and MMS remain incompletely understood but may involve hemodynamic shifts, the toxic effect of anti-TSH receptor antibodies, or shared genetic factors.

Summary

Barakat syndrome, also called HDR syndrome, is a rare genetic disorder encompassing hypoparathyroidism (H), sensorineural deafness (D) and renal disease (R). A 64-year-old woman was referred to our endocrinology clinic for a switch in treatment (from dihydrotachysterol to calcitriol). She had progressive sensorineural deafness since the age of 18 and idiopathic hypoparathyroidism diagnosed at age of 36. Her medical history included osteoporosis with hip/spine fractures, nephrolithiasis and a family history of hearing loss, osteoporosis and kidney disease. The patient’s clinical presentation indicated Barakat syndrome. Genetic analysis found a GATA3:c.916C>T nonsense variant. Further tests such as audiometry, labs and renal imaging supported the diagnosis. Due to rarity and manifold symptoms, diagnosis can be challenging. Optional GATA3 testing was suggested in 2018, except in cases of isolated sensorineural deafness or renal disease with pertinent family history. In isolated ‘H’ cases without ‘D’ and ‘R’, GATA3 studies are not required, as no haploinsufficiency cases were reported. Given the rise in genetic disorders, physicians should consistently consider rare genetic disorders in patients with suggestive symptoms, even decades after onset. Although diagnosis might not always impact management directly, it aids patients in accepting their condition and has broader family implications.

Learning points

• There is currently an important increase in genetic and clinical characterization of new orphan diseases and their causative agents.

• Unbiased re-evaluation for possible genetic disorders is necessary at every consultation.

• It is essential to recognize the differential diagnosis of idiopathic hypoparathyroidism.

• The patient’s clinical presentation and family history can be important to establish the correct diagnosis.

• Physicians should not hesitate to search a patient’s signs and symptoms online.

Summary

We report a case of catamenial erythema multiforme major in a 46-year-old female. She was treated successfully with goserelin, a GnRH agonist, until the expected age of menopause; however, its therapeutic effects persisted for longer than expected, possibly due to accumulation in adipose tissue.

Learning points

• A group of menstrual cycle-related dermatoses and hypersensitivity syndromes exist but are rarely reported in the literature.

• A history of recurrent cutaneous eruptions in premenopausal females should be considered in the context of the menstrual cycle.

• The diagnosis of menstrual cycle-related dermatoses is largely clinical, although provocation testing can assist.

• Treatment options are broad and are aimed at reducing the immune response and/or suppressing ovulation.

• Goserelin may accumulate and have a gonadotrophin-suppressing effect for longer than expected.

Summary

17α-hydroxylase deficiency (17α-OHD) is a rare form of congenital adrenal hyperplasia. We report the case of a teenage girl with 17α-OHD who presented with delayed puberty, hypergonadotropic hypogonadism and hypertension. We illustrate the clinical approach in workup, the subsequent management and monitoring of this rare condition.

Learning points

• 17α-hydroxylase deficiency (17α-OHD) should be considered as a rare yet important differential diagnosis of girls with delayed puberty and elevated gonadotropins.

• Urine steroid profile, plasma aldosterone and renin levels should be assessed in adolescent girls with hypergonadotropic hypogonadism, after the exclusion of more common conditions, e.g. Turner syndrome.

• Inhibiting deoxycorticosterone (DOC) release by partial glucocorticoid replacement, counteracting DOC’s mineralocorticoid effects by antagonists (such as eplerenone or spironolactone) as well as sex hormone replacements constitute the major backbone in the management of 17α-OHD.

Summary

Pancreatic dysgenesis (PD) is a rare congenital disease, with less than 100 cases reported in the literature. In most cases, patients are asymptomatic and the diagnosis is made incidentally. In this report, we present the case of two brothers with a history of intrauterine growth retardation, low birth weight, hyperglycemia, and poor weight gain. The diagnosis of PD and neonatal diabetes mellitus was made by an interdisciplinary team composed of an endocrinologist, a gastroenterologist, and a geneticist. Once the diagnosis was made, treatment with an insulin pump, pancreatic enzyme replacement therapy, and supplementation with fat-soluble vitamins was decided. The use of the insulin infusion pump facilitated the outpatient treatment of both patients.

Learning points

• Pancreatic dysgenesis is a relatively rare congenital anomaly; most of the time, patients are asymptomatic and are diagnosed incidentally.

• The diagnosis of pancreatic dysgenesis and neonatal diabetes mellitus should be made with an interdisciplinary team.

• Due to its flexibility, the use of an insulin infusion pump facilitated the management of these two patients.

Summary

Mpox (MPX) formerly known as monkeypox was declared a public health emergency of international concern, following an outbreak that commenced in May 2022. We report a case of subacute thyroiditis following MPX infection. To our knowledge, it is the first documented incidence of this complication in humans. A 51-year-old male, with a well-controlled human immunodeficiency virus (HIV) infection on antiretroviral therapy, was reviewed 3 weeks after a positive test for MPX. The acute skin lesions and initial systemic symptoms had resolved, but he described significant neck discomfort, fatigue, weight loss and night sweats. Blood tests showed a raised C-reactive protein, free T4 and suppressed thyroid-stimulating hormone. His thyroid antibodies were negative. He was treated initially with carbimazole and propranolol, pending exclusion of any other intercurrent infection. A chest radiograph was normal; blood cultures and a combined nose and throat swab for respiratory virus PCR testing were negative. Following this, he commenced a 2-week course of prednisolone; his symptoms resolved completely within 24 h of starting. He subsequently developed hypothyroidism, which was treated with levothyroxine. The clinical features, abnormal thyroid function, raised CRP and negative thyroid antibodies 3 weeks post-MPX positive test was consistent with viral subacute thyroiditis. This case demonstrates that, as described following other viral infections, MPX can cause subacute thyroiditis, which follows a similar course to the classic form of subacute thyroiditis. Clinicians should be aware of this potential endocrine complication when attending to patients with MPX.

Learning points

• Subacute thyroiditis can present following mpox virus infection.

• Its course is similar to the classic form of subacute thyroiditis and steroids are effective.

• It is important to exclude other concurrent infections prior to starting steroids, especially for patients who are immunosuppressed or in other high-risk groups.

Summary

We report a rare case of biopsy-proven isolated immunoglobulin G4 (IgG4)-related hypophysitis and Rathke’s cleft cyst (RCC) presenting as panhypopituitarism. A 54-year-old Caucasian female presented with symptoms of slurred speech, altered mental status, polyuria and polydipsia and was found to have panhypopituitarism. Brain MRI showed a suprasellar mass with suspected intralesional hemorrhage. She underwent trans-sphenoidal resection due to MRI evidence of compression of the optic chiasm and left optic nerve. Preoperatively, she was started on hydrocortisone, levothyroxine and desmopressin. Histopathology demonstrated a RCC with adjacent lymphoplasmacytic hypophysitis with numerous IgG4-immunoreactive plasma cells. Hydrocortisone was stopped at 10 months after confirming hypothalamic-pituitary-adrenal (HPA)-axis recovery and desmopressin was stopped at 1 year. There was recurrence of a cystic mass at 1 year follow-up. Over 4 years of follow-up, she continued to require levothyroxine, and the mass remained stable in size. In order to begin to understand how this case’s unique histopathological presentation influences clinical presentation, pituitary imaging and prognosis, we present an accompanying literature review.

Learning points

• Isolated IgG4 hypophysitis and coexisting Rathke’s cleft cyst is a rare condition, which presents a diagnostic challenge.

• Recognizing its characteristic features can assist with early recognition and initiation of therapy to promote optimal outcomes.

• Further studies investigating the mechanisms promoting co-occurrence of these entities and their effect on prognosis are needed.

Summary

Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication.

Learning points

• Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially.

• The incidence is 0.1–0.3% of all post Roux-en-Y gastric bypass patients.

• The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases.

• Pathological specimen of pancreas will show diffuse hypertrophy of beta cells.

• Management includes acarbose and total or subtotal pancreatectomy, which can be curative.

• With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.

Summary

A male phenotype accompanied by a 45,X karyotype is rare. It may occur due to Y chromosomal translocation or insertion to X/autosome. Clinical presentation may vary depending on the presence of the Y chromosomal locus and the degree of loss of autosome material. 45,X males can present with short stature and Turner syndrome phenotype due to haploinsufficiency of genes which are normally expressed in both X and Y chromosomes. The presence of the sex-determining region Y (SRY) gene leads to the differentiation of bipotential gonads to testis. Most individuals go through puberty normally, but some may need pubertal induction for delayed puberty. Rarely some can have a pubertal arrest. The risk of gonadoblastoma is minimal in these individuals due to functioning testicular tissue. The azoospermia factor (AZF) region is found on the long arm of the Yq chromosome and is needed for spermatogenesis. In a 45,X male with unbalanced translocation of Y chromosome, spermatogenesis can be affected due to the lack of AZF leading to Sertoli cell-only syndrome. This will have an implication on fertility in adult life. We present a 14-year-old boy with developmental delay, learning difficulties and subtle dysmorphic features who was diagnosed with 45,X,der(2)t(Y:2)(?:p25). Fluorescence in situ hybridisation analysis revealed translocation of SRY (Yp11.3) to the terminal part of the short arm of chromosome 2 resulting in the deletion of most of the Y chromosome (Yp11.2-q12) and part of chromosome 2(2p25.3). This is the first case where SRY translocation to chromosome 2 presents with the above clinical presentation.

Learning points

• 45,X karyotype is rare in male.

• It may occur due to SRY translocation or an insertion to X/autosome.

• SRY gene translocation to chromosome 2 has been not reported in the literature.

• Clinical presentation can be varied due to degree of loss of chromosomal material.

• Due to loss of AZF region found on the long arm of the Yq, spermatogenesis can be affected. Loss of 2p25 leads to learning difficulty and obesity.