Clinical course and management of pembrolizumab-associated isolated adrenocorticotrophic hormone deficiency: a new case and literature review

Immunotherapy ◽  
2021 ◽  
Author(s):  
Seda Hanife Oğuz ◽  
Uğur Ünlütürk ◽  
Sercan Aksoy ◽  
Tomris Erbas
Keyword(s):  
Clinical Symptoms ◽  
Hormone Deficiency ◽  
Bright Spot ◽  
Pituitary Hormone ◽  
Adrenocorticotrophic Hormone ◽  
Mri Findings ◽  
Acth Deficiency ◽  
Anterior Pituitary Hormone ◽  
Morning Cortisol ◽  
Symptoms And Signs

Hypophysitis is rarely reported in patients receiving pembrolizumab-only immunotherapies. Since the clinical presentation is usually as isolated adrenocorticotrophic hormone (ACTH) deficiency, patients may be misjudged as having clinical symptoms due to cancer or chemotherapy. A 49-year-old male with laryngeal cancer applied to our clinic just after the tenth cycle of his pembrolizumab treatment, with weakness and nausea/vomiting. Serum morning cortisol and ACTH were 0.47 mcg/dl and 10.1 pg/ml, respectively; the remaining anterior pituitary hormone levels were normal. Pituitary MRI revealed mild glandular enlargement and loss of posterior pituitary bright-spot. All symptoms and signs improved with low-dose prednisolone. This is the second reported case of pembolizumab-associated isolated ACTH deficiency having abnormal pituitary MRI findings as we have reviewed all reported cases in the literature.

scholarly journals A Large PROP1 Gene Deletion in a Turkish Pedigree

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Suheyla Gorar ◽  
Doga Turkkahraman ◽  
Kanay Yararbas
Keyword(s):  
Genetic Analysis ◽  
Empty Sella ◽  
Hormone Deficiency ◽  
Bright Spot ◽  
Pituitary Hormone ◽  
Coding Region ◽  
Gene Encoding ◽  
Acth Deficiency ◽  
Pituitary Hormone Deficiency ◽  
Prop1 Gene

Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multiple pituitary hormone deficiency. Alteration of the gene encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in a Turkish pedigree with three siblings who presented with short stature. Parents were first degree cousins. Index case, a boy, had somatotrope, gonadotrope, thyrotrope, and corticotrope deficiency. However, two elder sisters had somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph deficiency. On pituitary magnetic resonance, partial empty sella was detected with normal bright spot in all siblings. In genetic analysis, we found a gross deletion involving PROP1 coding region. In conclusion, we report three Turkish siblings with a gross deletion in PROP1 gene. Interestingly, although little boy with combined pituitary hormone deficiency has adrenocorticotropic hormone (ACTH) deficiency, his elder sisters with the same gross PROP1 deletion have no ACTH deficiency. This finding is in line with the fact that patients with PROP1 mutations may have different phenotype/genotype correlation.

scholarly journals Paediatric Langerhans Cell Histiocytosis Disease: Long-Term Sequelae in the Hypothalamic Endocrine System

2021 ◽  
pp. 1-9
Author(s):  
Elisa Vaiani ◽  
Guido Felizzia ◽  
Fabiana Lubieniecki ◽  
Jorge Braier ◽  
Alicia Belgorosky
Keyword(s):  
Anterior Pituitary ◽  
Langerhans Cell Histiocytosis ◽  
Endocrine System ◽  
Langerhans Cell ◽  
Hormone Deficiency ◽  
Bone Lesions ◽  
Pituitary Hormone ◽  
Multisystem Disease ◽  
Anterior Pituitary Hormone

Langerhans cell histiocytosis (LCH) is a disorder of the mononuclear phagocyte system that can affect almost any organ and system. The most common central nervous system (CNS) manifestation in LCH is the infiltration of the hypothalamic-pituitary region leading to destruction and neurodegeneration of CNS tissue. The latter causes the most frequent endocrinological manifestation, that is, central diabetes insipidus (CDI), and less often anterior pituitary hormone deficiency (APD). The reported incidence of CDI is estimated between 11.5 and 24% and is considered a risk factor for neurodegenerative disease and APD. Three risk factors for development of CDI are recognized in the majority of the studies: (1) multisystem disease, (2) the occurrence of reactivations or active disease for a prolonged period, and (3) the presence of craniofacial bone lesions. Since CDI may occur as the first manifestation of LCH, differential diagnosis of malignant diseases like germ cell tumours must be made. APD is almost always associated with CDI and can appear several years after the diagnosis of CDI. Growth hormone is the most commonly affected anterior pituitary hormone. Despite significant advances in the knowledge of LCH in recent years, little progress has been made in preventing long-term sequelae such as those affecting the hypothalamic-pituitary system.

Multiple Anterior Pituitary Hormone Deficiency

2009 ◽  
pp. 1363-1364
Author(s):  
Mark Oette ◽  
Marvin J. Stone ◽  
Hendrik P. N. Scholl ◽  
Peter Charbel Issa ◽  
Monika Fleckenstein ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Anterior Pituitary Hormone

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis

2016 ◽  
Vol 29 (7) ◽  
Author(s):  
Shunsuke Nakagawa ◽  
Yuichi Shinkoda ◽  
Daisuke Hazeki ◽  
Mari Imamura ◽  
Yasuhiro Okamoto ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Central Diabetes Insipidus ◽  
Pituitary Stalk ◽  
Hormone Deficiency ◽  
Late Relapse ◽  
Pituitary Hormone ◽  
Anterior Pituitary Hormone ◽  
The Central Nervous System

AbstractCentral diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

scholarly journals Idiopathic Hypophysitis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A588-A588
Author(s):  
Hafsa Amjed ◽  
Sobia Sadiq
Keyword(s):  
Thyroid Hormone ◽  
Hormone Replacement ◽  
Hormone Deficiency ◽  
Bright Spot ◽  
High Dose ◽  
Mri Findings ◽  
Central Hypothyroidism ◽  
Thyroid Hormone Replacement ◽  
Suprasellar Region ◽  
Secondary Hypothyroidism

Abstract Introduction: Hypophysitis is a heterogeneous condition that leads to inflammation of the sella / suprasellar region, potentially resulting in hormonal deficiencies or mass effects. Prevalence of hypophysitis ranges from 0.2% to 0.88%. Annual incidence of hypophysitis is 1 case per 9 million individuals. We present an interesting case of idiopathic hypophysitis. Clinical Case: A 52-year-old female was evaluated for secondary hypothyroidism. Patient complained of excess fatigue, weight gain, headaches, polyuria with nocturia and vision changes. She was seen by ophthalmology for formal visual field testing revealing right superior quadrantanopia. Labs significant for TSH 4 uIU/mL (ref range 0.27-4.2uIU/mL), FT4 0.72ng/dL (ref range 0.93-1.7 ng/dL), Anti TPO ab negative, AM cortisol 8.9UG/dL, ACTH 18pg/mL, IGF1 127ng/mL, prolactin 7ng/mL, FSH 102MIU/mL, LH 41 MIU/mL. MRI sella revealed homogenous enhancement of the pituitary with convex superior margin - 0.8*1*0.9cm concerning for hyperplasia. Due to the concern for hypophysitis, an extensive inflammatory workup was pursued which was negative. She was started on thyroid hormone replacement and DDAVP. An empiric trial of high dose steroids failed to provide any relief. During workup, patient complained of transient right sided face and arm tingling, diagnosed with TIA and started on aspirin. Due to worsening headaches, a pituitary biopsy was pursued. Pathology significant for glandular tissue ruling out inflammatory, neoplastic, and infectious etiologies. Neurology diagnosed the patient with hemicrania continua. Patient is currently maintained on thyroid hormone replacement and DDAVP with close follow-up. Discussion: The incidence of hypophysitis has recently increased due to increased awareness and also due to the use of medications like ICI. Primary hypophysitis is mostly due to autoimmune etiology. Secondary hypophysitis could result from infections, neoplastic conditions or an adverse effect of medications. Clinical presentations ranges from being asymptomatic to having features of hypopituitarism. Usually presents with mass effect, visual symptoms due to the upward expansion of the pituitary gland impinging the dura mater and optic chiasm. This is followed by symptoms of hormone deficiency, central DI and hyperprolactinemia. Central AI has been reported in 20%-75%, central hypogonadism in 15%-60%, central hypothyroidism in 25%-58%, GH deficiency in 5%-41%, and prolactin deficiency in 13%-25%. Typical MRI findings include, homogeneous pituitary contrast enhancement, pituitary stalk thickening and loss of posterior pituitary bright spot, ‘figure of 8’ appearance, ‘dural tail’. Treatment consists of surgery, anti-inflammatory medications, and radiotherapy. Glucocorticoid treatment is the cornerstone for medical management; however, the overall recurrence rate is high.

scholarly journals Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease

2020 ◽  
Vol 29 (10) ◽  
pp. 1648-1657 ◽  
Author(s):  
Hironori Bando ◽  
Peter Gergics ◽  
Brenda L Bohnsack ◽  
Kevin P Toolan ◽  
Catherine E Richter ◽  
...  
Keyword(s):  
Human Genetics ◽  
Clinical Symptoms ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Functional Evaluation ◽  
Loss Of Function ◽  
Sodium Influx ◽  
Large Numbers ◽  
Vertebrate Model ◽  
Rare Genetic Variants

Abstract Combined pituitary hormone deficiency (CPHD) is a genetically heterogeneous disorder caused by mutations in over 30 genes. The loss-of-function mutations in many of these genes, including orthodenticle homeobox 2 (OTX2), can present with a broad range of clinical symptoms, which provides a challenge for predicting phenotype from genotype. Another challenge in human genetics is functional evaluation of rare genetic variants that are predicted to be deleterious. Zebrafish are an excellent vertebrate model for evaluating gene function and disease pathogenesis, especially because large numbers of progeny can be obtained, overcoming the challenge of individual variation. To clarify the utility of zebrafish for the analysis of CPHD-related genes, we analyzed the effect of OTX2 loss of function in zebrafish. The otx2b gene is expressed in the developing hypothalamus, and otx2bhu3625/hu3625 fish exhibit multiple defects in the development of head structures and are not viable past 10 days post fertilization (dpf). Otx2bhu3625/hu3625 fish have a small hypothalamus and low expression of pituitary growth hormone and prolactin (prl). The gills of otx2bhu3625/hu3625 fish have weak sodium influx, consistent with the role of prolactin in osmoregulation. The otx2bhu3625/hu3625 eyes are microphthalmic with colobomas, which may underlie the inability of the mutant fish to find food. The small pituitary and eyes are associated with reduced cell proliferation and increased apoptosis evident at 3 and 5 dpf, respectively. These observations establish the zebrafish as a useful tool for the analysis of CPHD genes with variable and complex phenotypes.

scholarly journals Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic–pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests

2005 ◽  
Vol 152 (5) ◽  
pp. 735-741 ◽  
Author(s):  
M Maghnie ◽  
E Uga ◽  
F Temporini ◽  
N Di Iorgi ◽  
A Secco ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Adrenal Insufficiency ◽  
Low Dose ◽  
Clinical Symptoms ◽  
Adrenal Function ◽  
Hormone Deficiency ◽  
Cortisol Response ◽  
Normal Response ◽  
Morning Cortisol

Objectives: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic–pituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic–pituitary–adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences. Design and methods: In this study we evaluated the integrity of the HPA in 24 patients (age 4.2–31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency. Results: At a cortisol cut-off for a normal response of 550 nmol/l (20 μg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2–135.2 nmol/l (2.4–4.9 μg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST. Conclusion: We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re–assessment of adrenal function.

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