Clinical Overview > Hormone > ACTH
You are looking at 71 - 80 of 80 items
Search for other papers by Maura Bucciarelli in
Google Scholar
PubMed
Search for other papers by Ya-Yu Lee in
Google Scholar
PubMed
Search for other papers by Vasudev Magaji in
Google Scholar
PubMed
Summary
Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure.
Learning points
-
Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.
-
Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.
-
Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone.
Search for other papers by Chrisanthi Marakaki in
Google Scholar
PubMed
Search for other papers by Anna Papadopoulou in
Google Scholar
PubMed
Search for other papers by Olga Karapanou in
Google Scholar
PubMed
Search for other papers by Dimitrios T Papadimitriou in
Google Scholar
PubMed
Search for other papers by Kleanthis Kleanthous in
Google Scholar
PubMed
Search for other papers by Anastasios Papadimitriou in
Google Scholar
PubMed
Summary
11β-hydroxylase deficiency (11β-OHD), an autosomal recessive inherited disorder, accounts for 5–8% of congenital adrenal hyperplasia. In Greece, no cases of 11β-OHD have been described so far. The patient presented at the age of 13 months with mild virilization of external genitalia and pubic hair development since the age of 3 months. Hormonal profile showed elevated 11-deoxycortisol, adrenal androgens and ACTH levels. ACTH stimulation test was compatible with 11β-OHD. DNA of the proband and her parents was isolated and genotyped for CYP11B1 gene coding cytochrome P450c11. The girl was found to be compound heterozygous for two CYP11B1 novel mutations, p.Ala386Glu (exon 7), inherited from the father and p.Leu471Argin (exon 9) from the mother. Hydrocortisone supplementation therapy was initiated. Four years after presentation she remains normotensive, her growth pattern is normal and the bone age remains advanced despite adequate suppression of adrenal androgens.
Learning points
-
11β-hydroxylase (CYP11B1) deficiency (11OHD; OMIM +202010) is the second most common cause of CAH accounting for approximately 5–8% of cases with an incidence of 1:100 000–1:200 000 live births in non-consanguineous populations.
-
Two CYP11B1 inactivating novel mutations, p.Ala386Glu and p.Leu471Arg are reported
-
Regarding newborn females, in utero androgen excess results in ambiguous genitalia, whereas in the male newborn diagnosis may go undetected. In infancy and childhood adrenal androgen overproduction results in peripheral precocious puberty in boys and various degrees of virilization in girls.
-
Accumulation of 11-deoxycorticosterone and its metabolites causes hypertension in about two thirds of patients.
-
Diagnosis lies upon elevated 11-deoxycortisol and DOC plus upstream precursors, such as 17α-hydroxyprogesterone and Δ4-androstenedione.
-
The established treatment of steroid 11β-OHD is similar to that of steroid 21-hydroxylase deficiency and consists of glucocorticoid administration in order to reduce ACTH-driven DOC overproduction resulting in hypertension remission and improvement of the virilization symptoms.
Search for other papers by Annika Sjoeholm in
Google Scholar
PubMed
Search for other papers by Cassandra Li in
Google Scholar
PubMed
Search for other papers by Chaey Leem in
Google Scholar
PubMed
Search for other papers by Aiden Lee in
Google Scholar
PubMed
Search for other papers by Maria P Stack in
Google Scholar
PubMed
Search for other papers by Paul L Hofman in
Google Scholar
PubMed
Paediatric Endocrinology, Southern District Health Board, Dunedin, New Zealand
Search for other papers by Benjamin J Wheeler in
Google Scholar
PubMed
Summary
Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.
Learning points
-
Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.
-
The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.
-
As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.
-
Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.
Search for other papers by Verena Schwetz in
Google Scholar
PubMed
Search for other papers by Felix Aberer in
Google Scholar
PubMed
Search for other papers by Claudia Stiegler in
Google Scholar
PubMed
Search for other papers by Thomas R Pieber in
Google Scholar
PubMed
Search for other papers by Barbara Obermayer-Pietsch in
Google Scholar
PubMed
Search for other papers by Stefan Pilz in
Google Scholar
PubMed
Summary
Cushing's syndrome (CS) due to ectopic ACTH production accounts for about 10% of all types of CS and is frequently associated with metabolic alkalosis. Treatment of CS involves surgical resection and/or medical therapy to control hypercortisolism. We present the case of an 80-year-old woman affected by CS due to an unknown cause. The patient had severe metabolic alkalosis with refractory hypokalemia. To treat the underlying CS, fluconazole was initiated due to unavailability of ketoconazole. In spite of markedly decreasing cortisol levels, metabolic alkalosis persisted. Treatment of metabolic alkalosis with acetazolamide was thus initiated and pH levels successfully lowered. This case report shows that hypercortisolism can be effectively treated with fluconazole in cases where ketoconazole is unavailable or not tolerated and that persistent severe metabolic alkalosis caused by glucocorticoid excess can be safely and successfully treated with acetazolamide.
Learning points
-
Hypercortisolism can be effectively treated with fluconazole where ketoconazole is unavailable or not tolerated.
-
Glucocorticoid excess can cause severe metabolic alkalosis.
-
Persistent severe metabolic alkalosis can be safely and successfully treated with acetazolamide.
Search for other papers by Gabriela Alejandra Sosa in
Google Scholar
PubMed
Search for other papers by Soledad Bell in
Google Scholar
PubMed
Search for other papers by Silvia Beatriz Christiansen in
Google Scholar
PubMed
Search for other papers by Marcelo Pietrani in
Google Scholar
PubMed
Search for other papers by Mariela Glerean in
Google Scholar
PubMed
Search for other papers by Monica Loto in
Google Scholar
PubMed
Search for other papers by Soledad Lovazzano in
Google Scholar
PubMed
Search for other papers by Antonio Carrizo in
Google Scholar
PubMed
Search for other papers by Pablo Ajler in
Google Scholar
PubMed
Search for other papers by Patricia Fainstein Day in
Google Scholar
PubMed
Summary
IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis.
Learning points
-
IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.
-
It is more common in older men, but young women may also present this type of hypophysitis.
-
Although involvement of other organs is frequent, isolated pituitary disease is possible.
-
Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.
-
The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.
-
Glucocorticoids are recommended as first-line therapy.
Search for other papers by Satoru Sakihara in
Google Scholar
PubMed
Search for other papers by Kazunori Kageyama in
Google Scholar
PubMed
Search for other papers by Satoshi Yamagata in
Google Scholar
PubMed
Search for other papers by Ken Terui in
Google Scholar
PubMed
Search for other papers by Makoto Daimon in
Google Scholar
PubMed
Search for other papers by Toshihiro Suda in
Google Scholar
PubMed
Summary
ACTH-dependent Cushing's syndrome includes Cushing's disease and ectopic ACTH syndrome (EAS). The differential diagnosis of Cushing's disease from EAS in cases of ACTH-dependent Cushing's syndrome is a challenging problem. We report here a case of EAS with an unknown source of ACTH secretion. Extensive imaging procedures, involving computed tomography (neck to pelvis), pituitary magnetic resonance imaging, and whole-body 18F-fluorodeoxyglucose-positron emission tomography, failed to reveal the source of ACTH secretion. Intermittent administration of bromocriptine, a short-acting and nonselective dopamine agonist, has afforded adequate suppression of plasma ACTH and cortisol levels over the long term.
Learning points
-
Tumor excision is the primary treatment for EAS. However, when surgery is impossible, medical therapy is needed to treat hypercortisolism.
-
In cases where the source of ACTH secretion is unknown, inhibitors of steroidogenesis, such as metyrapone, mitotane, ketoconazole, and etomidate, are mostly used to suppress cortisol secretion.
-
Medications that suppress ACTH secretion are less effective, therefore less popular, as standard treatments.
-
In the present case, short-term treatment with dopamine agonists was effective for the long-term suppression of both ACTH and cortisol levels.
Search for other papers by M Baxter in
Google Scholar
PubMed
Search for other papers by S Gorick in
Google Scholar
PubMed
Search for other papers by F M Swords in
Google Scholar
PubMed
Summary
Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis.
Learning points
-
Partial recovery from Addison's disease is possible although uncommon.
-
Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.
-
As further reports of adrenal axis recovery emerge, this may influence the counselling given to patients with Addison's disease in the future.
Search for other papers by F Serra in
Google Scholar
PubMed
Search for other papers by S Duarte in
Google Scholar
PubMed
Search for other papers by S Abreu in
Google Scholar
PubMed
Search for other papers by C Marques in
Google Scholar
PubMed
Search for other papers by J Cassis in
Google Scholar
PubMed
Search for other papers by M Saraiva in
Google Scholar
PubMed
Summary
Ectopic secretion of ACTH is an infrequent cause of Cushing's syndrome. We report a case of ectopic ACTH syndrome caused by a nasal paraganglioma, a 68-year-old female with clinical features of Cushing's syndrome, serious hypokalaemia and a right paranasal sinus' lesion. Cranial magnetic resonance image showed a 46-mm mass on the right paranasal sinuses. Endocrinological investigation confirmed the diagnosis of ectopic ACTH production. Resection of the tumour normalised ACTH and cortisol secretion. The tumour was found to be a paraganglioma through microscopic analysis. On follow-up 3 months later, the patient showed nearly complete clinical recovery. Ectopic ACTH syndrome due to nasal paraganglioma is extremely uncommon, as only two other cases have been discussed in the literature.
Learning points
-
Ectopic Cushing's syndrome accounts for 10% of Cushing's syndrome etiologies.
-
Most paraganglioma of the head and neck are not hormonally active.
-
Nasal paraganglioma, especially ACTH producing, is a very rare tumour.
Search for other papers by Rajesh Rajendran in
Google Scholar
PubMed
Search for other papers by Sarita Naik in
Google Scholar
PubMed
Search for other papers by Derek D Sandeman in
Google Scholar
PubMed
Search for other papers by Azraai B Nasruddin in
Google Scholar
PubMed
Summary
We report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease.
Learning points
-
Plurihormonal pituitary adenomas are rare and unusual.
-
Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.
-
Pasireotide holds potential where conventional somatostatin analogues are not effective in acromegaly due to higher affinity for somatostatin receptor subtypes 1, 2, 3 and 5.
-
Significant deterioration in glycaemic control remains a concern in the use of pasireotide.
-
Currently, long-term safety and efficacy of pasireotide in patients with acromegaly and/or Cushing's disease are not fully clear.
Search for other papers by M Nwokolo in
Google Scholar
PubMed
Search for other papers by J Fletcher in
Google Scholar
PubMed
Summary
A 46-year-old woman presented multiple times in a 4-month period with hypotension, sepsis, hypoglycaemia and psychosis. A low random cortisol in combination with her presenting complaint made adrenal insufficiency the likely diagnosis. Fluid resuscitation and i.v. steroid therapy led to clinical improvement; however, a short synacthen test (SST) demonstrated an apparently satisfactory cortisol response. The test was repeated on a later admission and revealed a peak cortisol level of 25 nmol/l (>550 nmol/l). Concurrent treatment with i.v. hydrocortisone had led to a false-negative SST. ACTH was <5 ng/l (>10 ng/l), indicating secondary adrenal failure. We discuss the challenges surrounding the diagnosis of adrenal insufficiency and hypopituitarism, the rare complication of psychosis and a presumptive diagnosis of autoimmune lymphocytic hypophysitis (ALH).
Learning points
-
Adrenocortical insufficiency must be considered in the shocked, hypovolaemic and hypoglycaemic patient with electrolyte imbalance. Rapid treatment with fluid resuscitation and i.v. corticosteroids is vital.
-
Polymorphic presentations to multiple specialities are common. Generalised myalgia, abdominal pain and delirium are well recognised, psychosis is rare.
-
A random cortisol can be taken with baseline bloods. Once the patient is stable, meticulous dynamic testing must follow to confirm the clinical diagnosis.
-
The chronic disease progression of ALH is hypothesised to be expansion then atrophy of the pituitary gland resulting in empty sella turcica and hypopituitarism.
-
If hypopituitarism is suspected, an ACTH deficiency should be treated prior to commencing thyroxine (T4) therapy as unopposed T4 may worsen features of cortisol deficiency.