Summary

Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the NR5A1 gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the NR5A1 gene. A retrospective evaluation of the medical history, physical examination, limited endocrinological laboratory analysis and genetic analysis with DSD gene panel testing was performed. A 1.5-month-old individual was referred with ambiguous genitalia. The karyotype was 46,XY. The endocrinological analyses were within normal male reference including a normal response of cortisol within an adrenocorticotropic hormone test. A novel heterozygous missense variant c.206G>C p.(Arg69Pro) in the NR5A1 gene was detected. This variant was present in mosaic form (~20%) in his unaffected father. Because another missense variant at the same position and other missense variants involving the same highly conserved codon have been reported, we consider this NR5A1 variant in this 46,XY DSD patient as likely pathogenic in accordance with the ACMG/AMP 2015 guidelines causing ambiguous genitalia but no adrenal insufficiency. This variant was inherited from the apparently unaffected mosaic father, which might have implications for the recurrence risk in this family.

Learning points

• The importance of performing trio (patient and parents) sequencing is crucial in pointing out the origin of inheritance.

• In a 46,XY differences of sex development patient, a normal adrenal function does not rule out an NR5A1 mutation.

• With the support of a dedicated overseas institute partnership, we could solve this complex clinical case by molecular diagnosis in a resource-limited setting.

Summary

Myxedema coma is a severe complication of hypothyroidism, commonly affecting women over 60 years of age, causing slow, progressive multi-organ dysfunction, and mental deterioration. Due to improved diagnostics and treatment of hypothyroidism, myxedema coma has become uncommon. However, it is hardly reported in resource-limited settings. We present an elderly female with a history of total thyroidectomy due to multi-nodular goiter. She presented with features of heart failure, excessive weight gain, and cold sensation. Although the patient was on levothyroxine replacement therapy, her laboratory tests were suggestive of overt primary hypothyroidism. During the course of her hospitalization, she developed subcutaneous bleeding with frank hematuria. This led to an altered mental state and hypotension that were suggestive of myxedema coma. Stroke and pulmonary embolism were ruled out as potential differential diagnoses of her current state. She was treated with a high dose of oral levothyroxine followed by 150 μg of oral levothyroxine daily, which resulted in a favorable outcome despite being a fatal emergency. She was also treated with intravenous hydrocortisone and furosemide. Oral thyroid hormone replacement may be an effective option in those resource-limited settings where intravenous thyroid hormone replacement is not available. However, early diagnosis and treatment with an adequate dose of thyroid hormones are crucial to achieve a favorable outcome.

Learning points

• Myxedema coma is an uncommon complication of hypothyroidism with a fatal outcome.

• The diagnosis of myxedema coma is based on clinical suspicion, especially in patients with hypothyroidism and in the presence of precipitating factors. Although diagnostic and scoring criteria based on clinical, laboratory, and imaging features have been proposed, no consensus has been reached.

• This article shows an alternative treatment option for myxedema coma using oral levothyroxine, which led to a favorable outcome.

Summary

Acromegaly is a rare disease caused by hypersecretion of the growth hormone (GH). Most cases are caused by either pituitary microadenoma or macroadenoma. The GH producing tumors present with clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumor. The physical changes are usually slow and, therefore, recognition of the disease is delayed. These adenomas are never malignant but can have significant morbidity and mortality. A subgroup of patients with acromegaly present with severe hyperglycemia resulting in diabetic ketoacidosis (DKA) which requires insulin. Rarely are pituitary tumors responsible for generalized convulsions except when they are too large. We hereby present two cases, the first is that of a 26-year-old female who presented with new onset status epilepticus, DKA with a 1-year history of diabetes mellitus (DM). On examination, she had clinical features of acromegaly. The second case is that of a 34-year-old female who presented with new onset status epilepticus, hyperglycemia with a history of recently diagnosed DM, and features of gigantism. In both cases, their diagnosis was confirmed by elevated serum GH and later by elevated insulin-like growth factor type 1 levels, and CT of the head demonstrating large pituitary macroadenoma. The importance of clinical history and examination, as well as investigations is vital in the recognition of acromegaly. The prognosis of acromegalic patients depends on early clinical recognition and tumor size reduction by either medical or surgical therapy.

Learning points

• Conditions such as status epilepticus and DKA may be clinical presentations in patients presenting with acromegaly.

• Seizures are rare in people with pituitary adenoma and typically occur when the tumor invades the suprasellar area due to mass effect on the brain.

• This article shows how best we were able to manage the acromegaly complications in a low resource setting.

• Hyperprolactinemia in acromegaly may be due to disruption of the normal dopaminergic inhibition of prolactin secretion due to mass effect of the macroadenoma, and around 25% of GH-secreting adenomas co-secrete prolactin.