Isolated ACTH deficiency associated with Crohn's disease

We report a case of a 37-yr-old man with a 11-yr history of Crohn's disease (CD), who presented with mucous diarrheas of 1-week duration and a 3-month history of anorexia, increasing fatigue and weight loss of 7 kg. The patient was treated with sulfasalazine 3 g/day until 2 weeks prior to the present admission, when he reduced the dose to half as he considered the drug responsible for his symptoms. Despite aggressive iv rehydration and resolution of diarrheas with an increase in sulfasalazine dose, the patient remained hemodynamically unstable, while laboratory results showed anemia, hypoglycemia, hypertransaminasemia and hyponatremia with marked natriuresis. Thyroid function tests were consistent with primary hypothyroidism, without evidence of autoimmunity. Further laboratory investigation revealed a low basal cortisol and undetectable ACTH with preserved secretory responses of the other trophic pituitary hormones, establishing the diagnosis of isolated ACTH deficiency. Hydrocortisone replacement treatment induced a clinical and laboratory improvement. The autoimmune basis of isolated ACTH deficiency is discussed in association with the presumed contribution of immunologic reactions in the pathogenesis of CD. However more evidence is needed before isolated ACTH deficiency is added to the list of extraintestinal manifestations of CD.     

Isolated ACTH deficiency

Isolated ACTH deficiency is a rare disorder. We report four cases of this disease which presented to the Department of Endocrinology at Leeds General Infirmary over a one-year period. The diagnostic clinical and biochemical features of each case are discussed and the pertinent literature is reviewed. The clinical investigations vary somewhat between cases as the four patients presented in markedly different ways. Well validated dynamic endocrine investigations were employed including glucagon stimulation test (GST) and the corticotrophin releasing hormone (CRH) test (using 100 micrograms of human CRH with samples for ACTH and cortisol). Two patients probably had CRH deficiency and two had ACTH deficiency. All the cases are instructive, illustrating different features of this heterogeneous condition. We conclude that the diagnosis of this condition may be difficult due to the varied clinical presentation. We suggest that it is commoner than previously thought and that the precision of diagnosis can be improved using the CRH test.     

Isolated ACTH deficiency with transitory GH deficiency

A nine-year-old girl, who presented with a severe hypoglycemic coma, proved to have isolated ACTH deficiency, a finding previously reported in only two children. On the initial evaluation, before any treatment, GH did not respond to provocative stimuli. On replacement therapy with hydrocortisone, normal linear growth was observed. Repeated testing while on glucocorticoids replacement four years after the initial attack revealed normal GH response to stimulation test. It is suggested that cortisol deficiency was responsible for the severe hypoglycemic coma and subnormal GH response. A similar mechanism is speculated for the normal growth observed in some patients with apparent deficiency of anterior pituitary hormones, including GH. The possibility of permanent ACTH deficiency and transitory GH deficiency following hypophysitis is discussed.     

DiGeorge syndrome with Graves' disease: A case report

DiGeorge syndrome (DGS) is characterized by aplasia or hypoplasia of the thymus and parathyroid glands, cardiac defects and anomaly face. This syndrome is usually associated with hypocalcemia resulting from hypoparathyroidism. In most cases the initial symptom is tetany caused by hypocalcemia within 24-48 hours after birth, with symptoms by immune abnormality appearing later. We report a woman who passed with no symptoms before age 18 and was diagnosed DiGeorge syndrome by tetany with developing auto-immune thyroid disease (Graves' disease). She had surgery for intraventricular septal defect at age 3, hypoparathyroidism, decrease of T cells in peripheral blood and the deletion of the 22nd chromosome long arm (22q11.2). It is supposed that abnormalities of immune function of this case are not complete as indicated by complicating of Graves' disease, and contributing to her long-term survival.     

Thyroid hemiagenesis associated with Graves' disease and Graves' ophthalmopathy: case report.

Failure of embryologic development of a lobe of the thyroid gland is a rare anomaly. Usually, this condition is diagnosed when there are some other pathologic conditions in the gland and is often found when a patient presents with a thyroid nodule, which in reality is compensatory hypertrophy of the side that is present, therefore appearing as a nodule. A variety of pathological conditions occur in the remaining thyroid tissue in association with this rare anomaly such as adenoma, carcinoma, subacute thyroiditis, colloid nodule, Graves' disease, simple goiter, and Hashimoto thyroiditis. Association of Graves' disease with ophthalmopathy and thyroid hemiagenesis is quite rare and very few cases are reported in the literature. We report a 29-year-old female presented as Graves' disease and Graves' ophthalmopathy with left lobe hemiagenesis of the thyroid gland.     

Isolated ACTH deficiency confirmed by ACTH radioimmunoassay

A 28 year old woman presented with symptoms and biochemical findings suggesting hypoglycemia. Detailed endocrine investigations indicated secondary adrenocortical insufficiency with no rise in plasma ACTH or plasma cortisol following insulin-induced hypoglycemia or vasopressin infusion. The adrenal glands however produced cortisol normally following prolonged stimulation with depot tetracosactrin. Other anterior pituitary hormones were released normally following appropriate stimulation tests. The literature on isolated ACTH deficiency is briefly reviewed, and this case represents one of the few reports in which the diagnosis has been substantiated by ACTH radioimmunoassays.     

Isolated congenital ACTH deficiency: a cleavage enzyme defect?

The pro-opiomelanocortin (POMC) gene encodes adreno-corticotrophin (ACTH) which is derived from precursors by proteolytic cleavage. Congenital, isolated ACTH deficiency is rare but may be familial and fatal. The aetiology is unknown though defects at both hypothalamus and adenohypophysis have been postulated. We have studied a female presenting with hypoglycaemia in the neonatal period. When studied at 6 weeks of age, ACTH was unmeasurable even after injection of corticotrophin releasing hormone (CRH,_₄₁). ACTH precursors, quantitated by two-site immunuradiometric assay, were clearly measurable prior to treatment and were stimulated by CRH, ₄, and suppressed by glucocorticoid administration. Concentrations of POMC, N-terminal pro-opiocortin (N-POC) and β-endorphin (β-EP) were within the normal adult range during glucocorticoid replacement therapy; ACTH and βMipotrophin remained undetectable. The secretion of glucagon, measured by radioimmunoassay, in response to hypoglycaemia was normal. By sequencing polymerase chain reaction products from the patient's genomic DNA, the entire coding region of the POMC gene was established to be normal. The results are compatible with a cleavage enzyme defect.     

Isolated ACTH deficiency: a heterogeneous disorder. Critical review and report of four new cases

Isolated adrenocorticotropin (ACTH) deficiency is a rare cause of secondary adrenocortical insufficiency. This review summarizes the clinical and laboratory features of 39 previously reported cases plus 4 new patients. The clinical manifestations of isolated ACTH deficiency are variable, nonspecific and similar to those seen in adrenocortical insufficiency of any cause. The diagnosis of isolated ACTH deficiency due to intrinsic pituitary disease is made unequivocally when all the following criteria are met: 1) low basal urinary 17-hydroxycorticosteroid (17-OHCS) levels with or without low basal plasma cortisol, 2) low or normal basal plasma ACTH, 3) stimulation of cortisol, 17-OHCS or both during prolonged ACTH administration, 4) lack of 17-OHCS elevation in response to metyrapone and 5) normal secretory indices of other pituitary hormones. Isolated ACTH deficiency secondary to suprapituitary (e.g., hypothalamic) dysfunction is also based upon the above criteria, but, in addition, is associated with stimulation of cortisol and ACTH secretion following vasopressin administration.     

Isolated ACTH deficiency and primary hypothyroidism

A patient presented with severe primary hypothyroidism and secondary adrenal insufficiency due to the isolated deficiency of ACTH. The diagnostic evidence suggests that both are of an autoimmune aetiology. Acquired isolated or unitrophic ACTH deficiency is a rare but definite cause of adrenal insufficiency. Additional case reports and autopsy studies describing acquired isolated ACTH deficiency associated with autoimmune thyroid disease have appeared in the literature suggesting that the association is more than coincidental. Combined thyroid and adrenal failure should not always be considered to be the result of combined end organ failure. Unitrophic isolated ACTH deficiency may coexist with primary hypothyroidism.     

Localized myxedema on the nasal dorsum in a patient with Graves' disease: report of a case

We report the case of a 56-year-old Japanese female with Graves' disease associated with localized myxedema on the nasal dorsum. The patient developed localized myxedema concomitantly with hyperthyroidism before antithyroid therapy was given. The lesion was totally removed surgically, as it was small and well circumscribed. Although unusual locations of localized myxedema have been reported elsewhere, there is to date no case of localized myxedema on the nasal dorsum without involvement of the pretibial area reported in the literature. We discuss this unique feature of our patient.     

Graves' disease with intractable diarrhea, chylous ascites, and chylothorax: a case report.

A 50-year-old woman was admitted to our hospital because of severe diarrhea, irritableness, and severe pitting edema of the legs. The patient had been well until 5 years before admission, when a tremor and tachycardia developed and a diagnosis of Graves' disease was made. Treatment with methimazole was effective in reducing her tremor and tachycardia; however, she was often nonadherent with her antithyroid medication because of improvement of her symptoms. On admission, a thyroid swelling, exophthalmos, a pleural effusion, and ascites were observed. The results of thyroid function tests (free triiodothyronine: 21.5 pg/mL; free thyroxine: 7.17 ng/dL; thyroid-stimulating hormone (TSH): <0.01 microIU/mL; TSH receptor antibodies: 95.9%) were consistent with Graves' disease. Biochemical analysis of pleural and ascitic fluid was consistent with chylothorax and chylous ascites, respectively. Serum calcium, total protein, and albumin were very low. Her symptoms and signs except severe diarrhea, edema, pleural effusion, and ascites disappeared after receiving intravenous drip infusion of fluid replacement, and methimazole and iodine. Because of malnutrition, she was given a high-calorie intravenous infusion. Three months after admission, her pleural effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia. An appropriate treatment of Graves' disease is crucial to avoid serious sequelae of longstanding, poorly controlled hyperthyroidism.     

Graves' ophthalmopathy and atrophic thyroiditis: a case report

Graves' ophthalmopathy (GO)--also known as thyroid-associated orbitopathy or ophthalmopathy--usually affects patients with Graves' disease. Antibodies stimulating the TSH receptor are thought to be involved in the pathogenesis of this important and disabling extra-thyroidal manifestation of Graves' disease. Less frequently, GO occurs in subjects who neither have nor have ever shown evidence of thyroid dysfunction ("euthyroid GO"), while the occurrence of GO in patients with autoimmune Hashimoto's thyroiditis is thought to be quite rare and has sporadically been reported. The late and abrupt occurrence of severe GO without hyperthyroidism in an 88-yr-old woman with primary myxedema due to atrophic thyroiditis must be considered as an exceptional event. In this patient, GO was combined with elevated titres of serum auto-antibodies directed against the TSH receptor, while serum levels of anti-thyroglobulin and thyroperoxidase antibodies were within the normal range or only occasionally slightly above the normal values.     

Isolated acquired ACTH deficiency and primary hypothyroidism: a short series and review

Idiopathic isolated ACTH deficiency, congenital or acquired, is rare. It may be found in association with primary hypothyroidism. Here we describe four cases of acquired idiopathic isolated ACTH deficiency illustrating its importance and variable presentation. All cases had a structurally normal pituitary gland and persistently normal residual pituitary function. Three cases had co-existing primary hypothyroidism. We discuss the protean presentation of this rare but important condition, its treatment, associations, and possible aetiologies.