Diagnosis and Treatment > Investigation > CRH stimulation
You are looking at 1 - 6 of 6 items
Search for other papers by Alessandro Rossini in
Google Scholar
PubMed
Search for other papers by Francesca Perticone in
Google Scholar
PubMed
Search for other papers by Laura Frosio in
Google Scholar
PubMed
Search for other papers by Marco Schiavo Lena in
Google Scholar
PubMed
Search for other papers by Roberto Lanzi in
Google Scholar
PubMed
Summary
ACTH-secreting pheochromocytoma is a very rare cause of Cushing’s syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We report the case of a 45-year-old female patient with a 3 cm, high-density, left adrenal mass, diagnosed as an ACTH-secreting pheochromocytoma. The biochemical sensitivity of the tumor to somatostatin analogues was tested by a 100 μg s.c. octreotide administration, which led to an ACTH and cortisol reduction of 50 and 25% respectively. In addition to alpha and beta blockers, preoperative approach to laparoscopic adrenalectomy included octreotide, a somatostatin analogue, together with ketoconazole, in order to achieve an adequate pre-surgical control of cortisol release. Histopathological assessment confirmed an ACTH-secreting pheochromocytoma expressing type 2 and 5 somatostatin receptors (SSTR-2 and -5).
Learning points:
-
ACTH-secreting pheochromocytomas represent a rare and severe condition, characterized by high morbidity and mortality risk.
-
Surgical removal of the adrenal mass is the gold standard treatment, but adequate medical therapy is required preoperatively to improve the surgical outcome and to avoid major complications.
-
Somatostatin analogs, in addition to other medications, may represent a useful therapeutic option for the presurgical management of selected patients.
-
In this sense, the octreotide challenge test is a useful tool to predict favorable therapeutic response to the treatment.
Search for other papers by Karen Decaestecker in
Google Scholar
PubMed
Search for other papers by Veerle Wijtvliet in
Google Scholar
PubMed
Search for other papers by Peter Coremans in
Google Scholar
PubMed
Search for other papers by Nike Van Doninck in
Google Scholar
PubMed
Summary
ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing’s syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing’s syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic–pituitary–axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing’s stigmata improved gradually.
Learning points:
-
Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity.
-
The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion.
-
Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children.
-
If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.
Search for other papers by Shunsuke Funazaki in
Google Scholar
PubMed
Search for other papers by Hodaka Yamada in
Google Scholar
PubMed
Search for other papers by Kazuo Hara in
Google Scholar
PubMed
Division of Endocrinology and Metabolism Division of Endocrinology and Metabolism, International University of Health and Welfare Hospital, Tochigi, Japan
Search for other papers by San-e Ishikawa in
Google Scholar
PubMed
Summary
Lymphocytic hypophysitis (LyH) has been known to be associated with pregnancy. We herein report the case of a 33-year-old woman who underwent vaginal delivery without massive bleeding at 40 weeks of gestation. Because of the presence of headache and terrible fatigue after childbirth, she visited our hospital. Severe hyponatremia (Na, 118 mEq/L) and visual field abnormality was noted upon examination. MRI revealed pituitary enlargement with a swollen pituitary stalk, albeit at low signal intensity. Basal pituitary hormone levels were all reduced and remained low after exogenous administration of hypothalamic-releasing hormones. She was diagnosed with LyH and was started on prednisolone 60 mg/day. A month later, her pituitary function had gradually improved together with a decrease in pituitary enlargement and recovery of her visual field. The dose of prednisolone was gradually reduced and finally withdrawn 27 months later. After prednisolone withdrawal, her pituitary function remained normal despite the absence of any hormonal replacement. A year later, she became pregnant without medication and delivered a second baby without LyH recurrence. Thereafter, her pituitary function has been normal for more than 5 years. Two valuable observations can be highlighted from the case. First, the patient completely recovered from LyH through prompt prednisolone therapy during its initial phase and had almost normal pituitary function. Second, after recovery from LyH, she was able to undergo spontaneous pregnancy and deliver a baby. We believe that reporting incidences of spontaneous pregnancy after complete normalization of pituitary function in patients with LyH is of great significance.
Learning points:
-
Females are more affected by LyH than males given its strong association with pregnancy.
-
LyH possesses characteristic findings on pituitary MRI.
-
Glucocorticoid therapy for LyH has been recommended as an effective treatment.
-
A history of previous pregnancies does not increase the risk of developing AH in subsequent pregnancies.
-
Early induction of high-dose prednisolone was therapeutically effective in treating LyH.
Search for other papers by Regina Streuli in
Google Scholar
PubMed
Search for other papers by Ina Krull in
Google Scholar
PubMed
Search for other papers by Michael Brändle in
Google Scholar
PubMed
Search for other papers by Walter Kolb in
Google Scholar
PubMed
Search for other papers by Günter Stalla in
Google Scholar
PubMed
Search for other papers by Marily Theodoropoulou in
Google Scholar
PubMed
Search for other papers by Annette Enzler-Tschudy in
Google Scholar
PubMed
Search for other papers by Stefan Bilz in
Google Scholar
PubMed
Summary
Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease.
Learning points:
-
The discrimination between a Cushing’s disease and ectopic Cushing’s syndrome is challenging and has many caveats.
-
Ectopic ACTH/CRH co-secreting tumors are very rare.
-
Dynamic tests as well as BIPSS may be compatible with Cushing’s disease in ectopic CRH-secretion.
-
High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.
-
Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing’s syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing’s syndrome and lead to further investigations.
Search for other papers by Harish Venugopal in
Google Scholar
PubMed
Search for other papers by Katherine Griffin in
Google Scholar
PubMed
Search for other papers by Saima Amer in
Google Scholar
PubMed
Summary
Resection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy.
Learning points
-
Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging.
-
Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence needs to be managed aggressively.
-
Bilateral adrenalectomy should be considered when medical treatment is ineffective or poorly tolerated.
-
Percutaneous adrenal ablation may be considered in patients who are otherwise unable to undergo bilateral adrenalectomy.
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.
