Familial Glucocorticoid Deficiency Presenting as Progressive Hyperpigmentation (original) (raw)
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Indian journal of endocrinology and metabolism, 2012
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by glucocorticoid deficiency, high ACTH levels and normal mineralocorticoid levels. FGD is caused due to defects in adrenocorticotropic hormone (ACTH) signaling. The defect can be caused by mutations in genes encoding the ACTH receptor (melanocortin 2 receptor) or its accessory protein. Here we report three siblings with FGD. The second in order of siblings presented at an age of 15 years with history of diffuse hyperpigmentation since childhood. Their parents were non consanguineous. The patients were hyperpigmented and taller compared with their parents. None of the siblings had ambiguous genitalia or neurological abnormalities. There was no history of tuberculosis in the family. Biochemical investigations revealed low serum cortisol (<1 μg/dl) and elevated plasma ACTH (>1250 pg/ml). Serum electrolytes, aldosterone, and plasma renin activity was normal. Based on the above mentioned ...
Journal of Medical Case Reports, 2012
Introduction: Familial glucocorticoid deficiency, or hereditary unresponsiveness to adrenocorticotropic hormone, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Here, we report the case of an 18-month-old Egyptian boy with familial glucocorticoid deficiency. Case presentation: An 18-month-old Egyptian boy was referred to our institution for evaluation of generalized hyperpigmentation of the body associated with recurrent convulsions; one of his siblings, who had died at the age of nine months, also had generalized hyperpigmentation of the body. The initial clinical examination revealed generalized symmetrical deep hyperpigmentation of the body as well as hypotonia, normal blood pressure and normal male genitalia. He had low blood glucose and cortisol levels, normal aldosterone and high adrenocorticotropic hormone levels. Based on the above mentioned data, a provisional diagnosis of familial glucocorticoid deficiency was made, which was confirmed by a molecular genetics study. Oral hydrocortisone treatment at a dose of 10 mg/m 2 /day was started. The child was followed up after two months of treatment; the hyperpigmentation has lessened in comparison with his initial presentation and his blood sugar and cortisol levels were normalized. Conclusion: Familial glucocorticoid deficiency is a rare, treatable disease that can be easily missed due to nonspecific presentations. The consequences of delayed diagnosis and treatment are associated with high rates of morbidity and mortality.
Familial Glucocorticoid Deficiency Presenting with Skin Hyperpigmentation: A Case Report
Journal of Krishna Institute of Medical Sciences University, 2019
Familial Glucocorticoid Deficiency (FGD) has high morbidity and mortality, if not diagnosed and managed in time. The patient is liable to have hypoglycaemia which could be complicated by seizure and brain damage. Also these patients if not treated appropriately; will have high risk of infections and failure to thrive. We report a case of FGD baby of full term, male, birth weight 3 kg and born by uneventful normal delivery. On the second day of life, the baby had hypoglycaemia and later he developed mucosal membrane and skin hyperpigmentation. Critical sample during the hypoglycemic episode showed low serum cortisol, high adrenocorticotropic hormone level, normal serum electrolytes and normal kidney function. Arare familial glucocorticoid deficiency was diagnosed in time by doing appropriate investigations; includes critical sample during hypoglycaemia and the case was managed successfully by hydrocortisone 5 mg orally once daily.
Journal of Medical Case Reports
Background: Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency. Most patients are diagnosed following episodes of hypoglycemia or convulsion. We report the case of an infant with familial glucocorticoid deficiency who presented with hyperpigmentation, gigantism, and motor developmental delay without documented hypoglycemia, convulsion, or circulatory collapse. Case presentation: A 10-month-old Sri Lankan Sinhalese baby boy born to consanguineous parents presented with generalized hyperpigmentation and overgrowth since birth. He had marginal gross motor developmental delay. His weight, length, and head circumference were above normal range for his age. Investigations revealed low serum cortisol and high adrenocorticotrophic hormone levels with no cortisol response following adrenocorticotropin stimulation. Serum electrolytes and aldosterone levels were normal. A diagnosis of familial glucocorticoid deficiency was made based on isolated glucocorticoid deficiency, hyperpigmentation, and tall stature. Conclusions: This case report highlights that glucocorticoid deficiency can present without documented hypoglycemia and circulatory collapse and a high degree of suspicion is needed in diagnosis.
Familial glucocorticoid deficiency with a point mutation in the ACTH receptor: a case report
Journal of Korean medical science, 2009
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but no mineralocorticoid deficiency. We report a 2 month-old boy of nonconsanguineous parents, presented with hyperpigmentation. Physical examination showed diffuse dark skin of body including, oral mucosa, gum, hands, nails and scrotum. Laboratory evaluation revealed low serum cortisol (0.3 microg/dL), with very high plasma ACTH level (18,000 pg/mL), and serum cortisol level did not increase after ACTH stimulation test. Serum sodium, potassium, plasma renin activity, aldosterone and 17-hydroxyprogesterone were normal. Sequence analysis of the ACTH receptor (MC2R) gene showed a homozygous mutation of D103N. Diagnosis of FGD was made and treatment started with oral hydrocortisone.
Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive potentially life-threatening condition, characterized by glucocorticoid deficiency, preserved aldosterone/renin secretion, and secondary rise in plasma adrenocorticotropic hormone level. This occurs due to either mutation in adrenocorticotropic receptor (25%, FGD Type-1) or in the MC2 receptor accessory protein (15%–20%). However, in about 50% patients, no identifiable mutations have been identified. Clinically, it manifests with weakness, fatigue, weight loss, anorexia, nausea, vomiting, diarrhea, abdominal pain, hypoglycemia, and hypothermia. Progressive mucocutaneous pigmentation is a conspicuous presentation. Repeated hypoglycemia may result in seizure, persistent neurological, severe mental disability, and even sudden death. Standard therapy is oral glucocorticoids (10–15 mg/m2). Patients and Results: Two familial cases of FGD were put on progressively increasing doses of oral glucocorticoids (10 mg, 15 mg, and 20 mg/m2/day, each for 6 weeks) to achieve the best response without any adverse effects. One patient had excellent improvement with 15 mg/ m2/day, and another required 20 mg/m2/day. The latter patient had excellent overall improvement with only moderate improvement in pigmentation. Conclusion: Glucocorticoids replacement with optimum dose is necessary in FGD to promote physical and neurological growth and to prevent adrenal crises, hypotension, hypoglycemia, and sudden death. Higher dose than mentioned in literature (15 mg/m2/day) may be required in selected cases. Mucocutaneous pigmentation may require even higher dose than we used. More studies are required.
Early diagnosis in familial glucocorticoid deficiency
Dermato-Endocrinology
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive condition, characterized by marked atrophy of zona fasiculata and reticalaris with preservation of zona glomerulosa. Out of more than 50 published cases, 18 patients died as a result of glucocorticoid insufficiency. The main objective of this report is to emphasize the early diagnosis and treatment in our 17 month-old patient. Her presenting features following an upper respiratory tract infection were hypoglycemia, seizures as well as deep hyperpigmentation of the limbs and lips. A low cortisol concentration, elevated ACTH level and normal electrolytes and aldosterone level all supported the diagnosis of primary glucocorticoid deficiency. Parents were counseled about the diagnosis, management and the lifelong requirement of steroids. FGD is an easily treatable disease when recognized but frequently missed due to a non-specific presentation. FGD is a treatable disease, delayed diagnosis and treatment can lead to significant morbidity.
The genetics of familial glucocorticoid deficiency
Best Practice & Research Clinical Endocrinology & Metabolism, 2009
Keywords: adrenal failure neonatal hypoglycaemia ACTH resistance melanocortin 2 receptor Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol andbecause of the failure of the negative feedback loop to the pituitary and hypothalamus -grossly elevated ACTH levels. About half of all cases result from mutations in the ACTH receptor (melanocortin 2 receptor) or from mutations in the melanocortin 2 receptor accessory protein (MRAP), but other genetic causes of this potentially lethal disorder remain to be discovered.