Clinical Overview > Hormone > ACTH
You are looking at 11 - 20 of 80 items
Search for other papers by Nicholas J Theis in
Google Scholar
PubMed
Search for other papers by Toby Calvert in
Google Scholar
PubMed
Search for other papers by Peter McIntyre in
Google Scholar
PubMed
Search for other papers by Stephen P Robertson in
Google Scholar
PubMed
Search for other papers by Benjamin J Wheeler in
Google Scholar
PubMed
Summary
Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome.
Learning points:
-
Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels.
-
The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects.
-
Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.
Search for other papers by Katta Sai in
Google Scholar
PubMed
Search for other papers by Amos Lal in
Google Scholar
PubMed
Search for other papers by Jhansi Lakshmi Maradana in
Google Scholar
PubMed
Search for other papers by Pruthvi Raj Velamala in
Google Scholar
PubMed
Search for other papers by Trivedi Nitin in
Google Scholar
PubMed
Summary
Mifepristone is a promising option for the management of hypercortisolism associated with hyperglycemia. However, its use may result in serious electrolyte imbalances, especially during dose escalation. In our patient with adrenocorticotropic hormone-independent macro-nodular adrenal hyperplasia, unilateral adrenalectomy resulted in biochemical and clinical improvement, but subclinical hypercortisolism persisted following adrenalectomy. She was started on mifepristone. Unfortunately, she missed her follow-up appointments following dosage escalation and required hospitalization at an intensive care level for severe refractory hypokalemia.
Learning points:
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 Isabella Lupi in
Google Scholar
PubMed
Search for other papers by Alessandro Brancatella in
Google Scholar
PubMed
Search for other papers by Mirco Cosottini in
Google Scholar
PubMed
Search for other papers by Nicola Viola in
Google Scholar
PubMed
Search for other papers by Giulia Lanzolla in
Google Scholar
PubMed
Search for other papers by Daniele Sgrò in
Google Scholar
PubMed
Search for other papers by Giulia Di Dalmazi in
Google Scholar
PubMed
Search for other papers by Francesco Latrofa in
Google Scholar
PubMed
Search for other papers by Patrizio Caturegli in
Google Scholar
PubMed
Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Summary
Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.
Learning points:
-
PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade.
-
Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities.
-
Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease.
-
PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases
Search for other papers by Misaki Aoshima in
Google Scholar
PubMed
Search for other papers by Koji Nagayama in
Google Scholar
PubMed
Search for other papers by Kei Takeshita in
Google Scholar
PubMed
Search for other papers by Hiroshi Ajima in
Google Scholar
PubMed
Search for other papers by Sakurako Orikasa in
Google Scholar
PubMed
Search for other papers by Ayana Iwazaki in
Google Scholar
PubMed
Search for other papers by Hiroaki Takatori in
Google Scholar
PubMed
Search for other papers by Yutaka Oki in
Google Scholar
PubMed
Summary
Patients treated with immunosuppressive drugs, especially methotrexate (MTX), rarely develop lymphoproliferative disorders (LPDs), known as MTX-related LPD (MTX–LPD). The primary site of MTX–LPD is often extranodal. This is the first reported case of MTX–LPD in the pituitary. A 65-year-old woman was admitted to our hospital with symptoms of oculomotor nerve palsy and multiple subcutaneous nodules. She had been treated with MTX for 11 years for rheumatoid arthritis. Computed tomography showed multiple masses in the orbit, sinuses, lung fields, anterior mediastinum, kidney, and subcutaneous tissue. Brain magnetic resonance imaging revealed a sellar mass. She was diagnosed with hypopituitarism and central diabetes insipidus based on endocrine examination. Although pituitary biopsy could not be performed, we concluded that the pituitary lesion was from MTX–LPD, similar to the lesions in the sinuses, anterior mediastinum, and subcutaneous tissue, which showed polymorphic LPD on biopsy. MTX was discontinued, and methylprednisolone was administered to improve the neurologic symptoms. After several weeks, there was marked improvement of all lesions, including the pituitary lesion, but the pituitary function did not improve. When pituitary lesions are caused by MTX–LPD, the possibility of anterior hypopituitarism and central diabetes insipidus needs to be considered. Further studies are needed to investigate the effectiveness of early diagnosis and treatment of MTX–LPD in restoring pituitary dysfunction.
Learning points
-
Pituitary lesions from MTX–LPD may cause hypopituitarism and central diabetes insipidus.
-
Pituitary metastasis of malignant lymphoma and primary pituitary lymphoma, which have the same tissue types with MTX–LPD, have poor prognosis, but the lesions of MTX–LPD can regress only after MTX discontinuation.
-
In cases of pituitary lesions alone, a diagnosis of MTX–LPD may be difficult, unless pituitary biopsy is performed. This possibility should be considered in patients treated with immunosuppressive drugs.
-
Pituitary hypofunction and diabetes insipidus may persist, even after regression of the lesions on imaging due to MTX discontinuation.
Search for other papers by Elke Thijs in
Google Scholar
PubMed
Search for other papers by Katrien Wierckx in
Google Scholar
PubMed
Search for other papers by Stefaan Vandecasteele in
Google Scholar
PubMed
Search for other papers by Annick Van den Bruel in
Google Scholar
PubMed
Summary
A 42-year-old man with complaints of muscle soreness and an increased pigmentation of the skin was referred because of a suspicion of adrenal insufficiency. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency (PAI) and treatment with hydrocortisone and fludrocortisone was initiated. An etiological workup, including an assessment for anti-adrenal antibodies, very long-chain fatty acids, 17-OH progesterone levels and catecholamine secretion, showed no abnormalities. 18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands and bilateral presence of an adrenal nodule, with 18fluorodeoxyglucose accumulation. A positive tuberculin test and positive family history of tuberculosis were found, and tuberculostatic drugs were initiated. During the treatment with the tuberculostatic drugs the patient again developed complaints of adrenal insufficiency, due to insufficient dosage of hydrocortisone because of increased metabolism of hydrocortisone.
Learning points:
-
Shrinkage of the adrenal nodules following tuberculostatic treatment supports adrenal tuberculosis being the common aetiology.
-
The tuberculostatic drug rifampicin is a CYP3A4 inducer, increasing the metabolism of hydrocortisone. Increase the hydrocortisone dosage upon initiation of rifampicin in case of (adrenal) tuberculosis.
-
A notification on the Addison’s emergency pass could be considered to heighten physician’s and patients awareness of hydrocortisone drug interactions.
Search for other papers by Sharmin Jahan in
Google Scholar
PubMed
Search for other papers by M A Hasanat in
Google Scholar
PubMed
Search for other papers by Tahseen Mahmood in
Google Scholar
PubMed
Search for other papers by Shahed Morshed in
Google Scholar
PubMed
Search for other papers by Raziul Haq in
Google Scholar
PubMed
Search for other papers by Md Fariduddin in
Google Scholar
PubMed
Summary
Silent corticotroph adenoma (SCA) is an unusual type of nonfunctioning pituitary adenoma (NFA) that is silent both clinically and biochemically and can only be recognized by positive immunostaining for ACTH. Under rare circumstances, it can transform into hormonally active disease presenting with severe Cushing syndrome. It might often produce diagnostic dilemma with difficult management issue if not thoroughly investigated and subtyped accordingly following surgery. Here, we present a 21-year-old male who initially underwent pituitary adenomectomy for presumed NFA with compressive symptoms. However, he developed recurrent and invasive macroadenoma with severe clinical as well as biochemical hypercortisolism during post-surgical follow-up. Repeat pituitary surgery was carried out urgently as there was significant optic chiasmal compression. Immunohistochemical analysis of the tumor tissue obtained on repeat surgery proved it to be an aggressive corticotroph adenoma. Though not cured, he showed marked clinical and biochemical improvement in the immediate postoperative period. Anticipating recurrence from the residual tumor, we referred him for cyber knife radio surgery.
Learning points:
-
Pituitary NFA commonly present with compressive symptoms such as headache and blurred vision.
-
Post-surgical development of Cushing syndrome in such a case could be either drug induced or endogenous.
-
In the presence of recurrent pituitary tumor, ACTH-dependent Cushing syndrome indicates CD.
-
Rarely a SCA presenting initially as NFA can transform into an active corticotroph adenoma.
-
Immunohistochemical marker for ACTH in the resected tumor confirms the diagnosis.
Search for other papers by Charlotte Delcourt in
Google Scholar
PubMed
Search for other papers by Halil Yildiz in
Google Scholar
PubMed
Search for other papers by Alessandra Camboni in
Google Scholar
PubMed
Search for other papers by Eric Van den Neste in
Google Scholar
PubMed
Search for other papers by Véronique Roelants in
Google Scholar
PubMed
Search for other papers by Alexandra Kozyreff in
Google Scholar
PubMed
Search for other papers by Jean Paul Thissen in
Google Scholar
PubMed
Search for other papers by Dominique Maiter in
Google Scholar
PubMed
Search for other papers by Raluca Maria Furnica in
Google Scholar
PubMed
Summary
A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of a sarcoidosis–lymphoma syndrome. The co-existence of these diseases constitutes a diagnostic challenge and we emphasize the necessity of exact staging of disease in order to prescribe adequate treatment.
Learning points:
-
The possibility of a sarcoidosis–lymphoma syndrome, although rare, should be kept in mind during evaluation for lymphadenopathies.
-
In the case of such association, lymphoma usually occurs after sarcoidosis. However, sarcoidosis and lymphoma can be detected simultaneously and development of sarcoidosis in a patient with previous lymphoma has also been reported.
-
An accurate diagnosis of the disease and the respective organ involvements, including biopsy, is necessary in order to prescribe adequate treatment.
Search for other papers by Joanna Prokop in
Google Scholar
PubMed
Search for other papers by João Estorninho in
Google Scholar
PubMed
Search for other papers by Sara Marote in
Google Scholar
PubMed
Search for other papers by Teresa Sabino in
Google Scholar
PubMed
Search for other papers by Aida Botelho de Sousa in
Google Scholar
PubMed
Search for other papers by Eduardo Silva in
Google Scholar
PubMed
Search for other papers by Ana Agapito in
Google Scholar
PubMed
Summary
POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes) is a rare multisystemic disease. Clinical presentation is variable, the only mandatory criteria being polyneuropathy and monoclonal gammapathy in association with one major and one minor criterion. Primary adrenal insufficiency is rarely reported. We describe a case of a 33-year-old patient, in whom the presenting symptoms were mandibular mass, chronic sensory-motor peripheral polyneuropathy and adrenal insufficiency. The laboratory evaluation revealed thrombocytosis, severe hyperkalemia with normal renal function, normal protein electrophoresis and negative serum immunofixation for monoclonal protein. Endocrinologic laboratory work-up confirmed Addison’s disease and revealed subclinical primary hypothyroidism. Thoracic abdominal CT showed hepatosplenomegaly, multiple sclerotic lesions in thoracic vertebra and ribs. The histopathologic examination of the mandibular mass was nondiagnostic. Bone marrow biopsy revealed plasma cell dyscrasia and confirmed POEMS syndrome. Axillary lymphadenopathy biopsy: Castleman’s disease. Gluco-mineralocorticoid substitution and levothyroxine therapy were started with clinical improvement. Autologous hematopoietic cell transplantation (HCT) was planned, cyclophosphamide induction was started. Meanwhile the patient suffered two ischemic strokes which resulted in aphasia and hemiparesis. Cerebral angiography revealed vascular lesions compatible with vasculitis and stenosis of two cerebral arteries. The patient deceased 14 months after the diagnosis. The young age at presentation, multiplicity of manifestations and difficulties in investigation along with the absence of serum monoclonal protein made the diagnosis challenging. We report this case to highlight the need to consider POEMS syndrome in differential diagnosis of peripheral neuropathy in association with endocrine abnormalities even in young patients.
Learning points:
-
POEMS syndrome is considered a ‘low tumor burden disease’ and the monoclonal protein in 15% of cases is not found by immunofixation.
-
Neuropathy is the dominant characteristic of POEMS syndrome and it is peripheral, ascending, symmetric and affecting both sensation and motor function.
-
Endocrinopathies are a frequent feature of POEMS syndrome, but the cause is unknown.
-
The most common endocrinopathies are hypogonadism, primary hypothyroidism and abnormalities in glucose metabolism.
-
There is no standard therapy; however, patients with disseminated bone marrow involvement are treated with chemotherapy with or without HCT.
Search for other papers by Stephanie Wei Ping Wong in
Google Scholar
PubMed
Search for other papers by Yew Wen Yap in
Google Scholar
PubMed
Search for other papers by Ram Prakash Narayanan in
Google Scholar
PubMed
Search for other papers by Mohammad Al-Jubouri in
Google Scholar
PubMed
Search for other papers by Ashley Grossman in
Google Scholar
PubMed
Search for other papers by Christina Daousi in
Google Scholar
PubMed
Search for other papers by Yahya Mahgoub in
Google Scholar
PubMed
Summary
We report our experience on managing a case of florid Cushing’s disease with Methicillin-resistant Staphylococcus aureus (MRSA) sepsis using intravenous etomidate in the intensive care unit of a UK district general hospital.
Learning points:
-
Severe Cushing’s syndrome is associated with high morbidity and mortality.
-
Etomidate is a safe and effective medical therapy to rapidly lower cortisol levels even in the context of severe sepsis and immunosuppression.
-
Etomidate should ideally be administered in an intensive care unit but is still feasible in a district general hospital.
-
During treatment with etomidate, accumulation of serum 11β-deoxycortisol (11DOC) levels can cross-react with laboratory cortisol measurement leading to falsely elevated serum cortisol levels. For this reason, serum cortisol measurement using a mass spectrometry assay should ideally be used to guide etomidate prescription.