Diagnosis and Treatment > Medication
Search for other papers by Mike Lin in
Google Scholar
PubMed
Cancer Genetics Unit, Kolling Institute of Medical Research, New South Wales, Australia
Faculty of Health and Medicine, University of Sydney, New South Wales, Australia
Search for other papers by Venessa Tsang in
Google Scholar
PubMed
Search for other papers by Janice Brewer in
Google Scholar
PubMed
Cancer Genetics Unit, Kolling Institute of Medical Research, New South Wales, Australia
Faculty of Health and Medicine, University of Sydney, New South Wales, Australia
Search for other papers by Roderick Clifton-Bligh in
Google Scholar
PubMed
Cancer Genetics Unit, Kolling Institute of Medical Research, New South Wales, Australia
Faculty of Health and Medicine, University of Sydney, New South Wales, Australia
Search for other papers by Matti L Gild in
Google Scholar
PubMed
Summary
Lymphocytic hypophysitis is a rare neuroendocrine disease characterised by an autoimmune inflammatory disorder of the pituitary gland. We report a 50-year-old woman who presented with headaches and bilateral sixth cranial nerve palsies. MRI of the pituitary revealed extensive fibrosis involving the sellar and extending into both cavernous sinuses causing bilateral occlusion of the internal carotid arteries (ICA). Transphenoidal biopsy confirmed the diagnosis of infiltrative fibrotic lymphocytic hypophysitis. Symptoms resolved with high dose of oral steroids but relapsed on tapering, requiring several treatments of i.v. pulse steroids over 8 months. Rituximab combined with mycophenolate mofetil was required to achieve long-term symptom relief. Serial MRI pituitary imaging showed stabilisation of her disease without reduction in sellar mass or regression of ICA occlusion. The patient’s brain remained perfused solely by her posterior circulation. This case demonstrates an unusual presentation of a rare disease and highlights a successful steroid-sparing regimen in a refractory setting.
Learning points:
-
Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. In exceptional cases, there is infiltration of the cavernous sinus with subsequent occlusion of the internal carotid arteries.
-
First-line treatment of lymphocytic hypophysitis is high-dose glucocorticoids. Relapse after tapering or discontinuation is common and its use is limited by long-term adverse effects.
-
There is a paucity of data for treatment of refractory lymphocytic hypophysitis. Goals of treatment should include improvement in symptoms, correction of hormonal insufficiencies, reduction in lesion size and prevention of recurrence.
-
Steroid-sparing immunosuppressive drugs such as rituximab and mycophenolate mofetil have been successful in case reports. This therapeutic combination represents a viable alternative treatment for refractory disease.
Search for other papers by Nirusha Arnold in
Google Scholar
PubMed
Search for other papers by Victor O’Toole in
Google Scholar
PubMed
Search for other papers by Tien Huynh in
Google Scholar
PubMed
Search for other papers by Howard C Smith in
Google Scholar
PubMed
Search for other papers by Catherine Luxford in
Google Scholar
PubMed
Search for other papers by Roderick Clifton-Bligh in
Google Scholar
PubMed
Westmead Teaching Hospital, Royal North Shore Teaching Hospital, The University of Sydney, Sydney, New South Wales, Australia
Search for other papers by Creswell J Eastman in
Google Scholar
PubMed
Summary
Parathyroid-independent hypercalcaemia of pregnancy, due to biallelic loss of function of the P450 enzyme CYP24A1, the principal inactivator of 1,25(OH)2D results in hypervitaminosis D, hypercalcaemia and hypercalciuria. We report two cases of this disorder, with intractable hypercalcaemia, one occurring during gestation and into the postpartum, and the other in the postpartum period. Case 1, a 47-year-old woman with a twin pregnancy conceived by embryo transfer, presented with hypercalcaemia at 23 weeks gestation with subnormal serum parathyroid hormone (PTH) and normal serum 25-OH D levels. She was admitted to hospital at 31 weeks gestation with pregnancy-induced hypertension, gestational diabetes and increasing hypercalcaemia. Caesarean section at 34 weeks gestation delivered two healthy females weighing 2.13 kg and 2.51 kg. At delivery, the patient’s serum calcium level was 2.90 mmol/L. Postpartum severe hypercalcaemia was treated successfully with Denosumab 60 mg SCI, given on two occasions. CYP24A1 testing revealed she was compound heterozygous for pathogenic variants c.427_429delGAA, (p.Glu143del) and c.1186C>T, (p.Arg396Trp). Case 2, a 36-year-old woman presented 4 days after the delivery of healthy twins with dyspnoea, bradycardia, severe headaches, hypertension and generalized tonic-clonic seizures after an uneventful pregnancy. She was hypercalcaemic with a suppressed PTH, normal 25(OH)D, and elevated 1,25(OH)2D levels. Her symptoms partially responded to i.v. saline and corticosteroids in the short term but bisphosphonates such as Pamidronate and Zoledronic acid did not result in sustained improvement. Denosumab 120 mg SCI successfully treated the hypercalcaemia which resolved completely 2 months post-partum. CYP24A1 testing revealed she was homozygous for the pathogenic variant c.427_429delGAA, (p.Glu143del).
Learning points:
-
Hypercalcaemia in pregnancy can be associated with considerable morbidity with few options available for management.
-
In non-PTH-related hypercalcaemia the diagnosis of CYP24A1 deficiency should be considered.
-
Making a definitive diagnosis of CYP24A1 deficiency by genetic testing delays the diagnosis, while the availability of serum 24,25-dihydroxyvitamin D (24,25(OH)2D) will expedite a diagnosis.
-
In pregnant women with CYP24A1 deficiency hypercalcaemia can worsen in the post-partum period and is more likely to occur with twin pregnancies but generally resolves within 2–3 months.
-
Therapeutic alternatives are limited in pregnancy and their effectiveness is short-lived and mostly ineffective. Denosumab used in both our patients after delivery was the most effective agent normalizing calcium and may have benefit as a long-term therapeutic agent in preventing complications in patients with CYP24A1 deficiency.
Search for other papers by Xin Feng in
Google Scholar
PubMed
Search for other papers by Gregory Kline in
Google Scholar
PubMed
Summary
In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.
Learning points:
-
Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.
-
Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.
-
Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.
Search for other papers by Lourdes Balcázar-Hernández in
Google Scholar
PubMed
Search for other papers by Guadalupe Vargas-Ortega in
Google Scholar
PubMed
Search for other papers by Yelitza Valverde-García in
Google Scholar
PubMed
Search for other papers by Victoria Mendoza-Zubieta in
Google Scholar
PubMed
Search for other papers by Baldomero González-Virla in
Google Scholar
PubMed
Summary
The craniopharyngiomas are solid cystic suprasellar tumors that can present extension to adjacent structures, conditioning pituitary and hypothalamic dysfunction. Within hypothalamic neuroendocrine dysfunction, we can find obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, imbalances in the regulation of body temperature, thirst, heart rate and/or blood pressure and alterations in dietary intake (like anorexia). We present a rare case of anorexia–cachexia syndrome like a manifestation of neuroendocrine dysfunction in a patient with a papillary craniopharyngioma. Anorexia–cachexia syndrome is a complex metabolic process associated with underlying illness and characterized by loss of muscle with or without loss of fat mass and can occur in a number of diseases like cancer neoplasm, non-cancer neoplasm, chronic disease or immunodeficiency states like HIV/AIDS. The role of cytokines and anorexigenic and orexigenic peptides are important in the etiology. The anorexia–cachexia syndrome is a clinical entity rarely described in the literature and it leads to important function limitation, comorbidities and worsening prognosis.
Learning points:
-
Suprasellar lesions can result in pituitary and hypothalamic dysfunction.
-
The hypothalamic neuroendocrine dysfunction is commonly related with obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, but rarely with anorexia–cachexia.
-
Anorexia–cachexia syndrome is a metabolic process associated with loss of muscle, with or without loss of fat mass, in a patient with neoplasm, chronic disease or immunodeficiency states.
-
Anorexia–cachexia syndrome results in important function limitation, comorbidities that influence negatively on treatment, progressive clinical deterioration and bad prognosis that can lead the patient to death.
-
Anorexia–cachexia syndrome should be suspected in patients with emaciation and hypothalamic lesions.
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, USA
Search for other papers by Jasmeet Kaur in
Google Scholar
PubMed
Augusta University School of Medicine, Augusta, Georgia, USA
Neonatology Intensive Care Unit, Memorial University Medical Center, Georgia, USA
Search for other papers by Alan M Rice in
Google Scholar
PubMed
Search for other papers by Elizabeth O’Connor in
Google Scholar
PubMed
Neonatology Intensive Care Unit, Memorial University Medical Center, Georgia, USA
Search for other papers by Anil Piya in
Google Scholar
PubMed
Search for other papers by Bradley Buckler in
Google Scholar
PubMed
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, USA
Search for other papers by Himangshu S Bose in
Google Scholar
PubMed
Congenital adrenal hyperplasia (CAH) is caused by mutations in cytochrome P450 side chain cleavage enzyme (CYP11A1 and old name, SCC). Errors in cholesterol side chain cleavage by the mitochondrial resident CYP11A1 results in an inadequate amount of pregnenolone production. This study was performed to evaluate the cause of salt-losing crisis and possible adrenal failure in a pediatric patient whose mother had a history of two previous stillbirths and loss of another baby within a week of birth. CAH can appear in any population in any region of the world. The study was conducted at Memorial University Medical Center and Mercer University School of Medicine. The patient was admitted to Pediatric Endocrinology Clinic due to salt-losing crisis and possible adrenal failure. The patient had CAH, an autosomal recessive disease, due to a novel mutation in exon 5 of the CYP11A1 gene, which generated a truncated protein of 286 amino acids compared with wild-type protein that has 521 amino acids (W286X). Although unrelated, both parents are carriers. Mitochondrial protein import analysis of the mutant CYP11A1 in steroidogenic MA-10 cells showed that the protein is imported in a similar fashion as observed for the wild-type protein and was cleaved to a shorter fragment. However, mutant’s activity was 10% of that obtained for the wild-type protein in non-steroidogenic COS-1 cells. In a patient of Mexican descent, a homozygous CYP11A1 mutation caused CAH, suggesting that this disease is not geographically restricted even in a homogeneous population.
Learning points:
-
Novel mutation in CYP11A1 causes CAH;
-
This is a pure population from Central Mexico;
-
Novel mutation created early truncated protein.
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia
Search for other papers by Beverly T Rodrigues in
Google Scholar
PubMed
Search for other papers by Zulfiquer Otty in
Google Scholar
PubMed
Search for other papers by Kunwarjit Sangla in
Google Scholar
PubMed
School of Medicine and Dentistry, James Cook University, Douglas, Queensland, Australia
Search for other papers by Vasant V Shenoy in
Google Scholar
PubMed
Summary
Autoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.
Learning points
-
AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.
-
It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.
-
Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.
-
Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.
-
Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.
-
Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.
Search for other papers by Kamel Mohammedi in
Google Scholar
PubMed
Search for other papers by Charbel Abi Khalil in
Google Scholar
PubMed
Search for other papers by Sophie Olivier in
Google Scholar
PubMed
Search for other papers by Imane Benabad in
Google Scholar
PubMed
Search for other papers by Ronan Roussel in
Google Scholar
PubMed
Search for other papers by Michel Marre in
Google Scholar
PubMed
Summary
Hypoglycemia is a common medical emergency. It is the most frequent complication induced by anti-diabetic treatment. However, it can be observed in other conditions unrelated to diabetes such as insulinoma, autoimmune disorders, and neoplasia. Herein, we report the case of a rare cause of severe and recurrent hypoglycemia in a 77-year-old woman with a malignant solitary fibrous tumor (MSFT). A 77-year-old woman was admitted to the emergency department for loss of consciousness induced by severe hypoglycemia. Her standard laboratory findings were unremarkable. HbA1c, albumin, renal, liver, thyroid, and adrenal function tests were normal. Cerebral CT scan was also normal. At the time of confirmed hypoglycemia, the serum level of insulin and C-peptide was low. On the basis of the past medical history and the absence of other comment etiologies, a paraneoplastic cause was suspected. Thus, the diagnosis of a non-islet cell tumor-induced hypoglycemia (NICTH) was established by the presence of incompletely processed precursors of IGF2 (big IGF2) in plasma electrophoresis. However, the IGF1 level was low. Therapy with corticosteroids improved hypoglycemia and clinical symptoms. NICTH is a rare cause of hypoglycemia. It should be considered in patients with mesenchymal or malignant epithelial tumors suffering from recurrent episodes of hypoglycemia. The diagnosis will be established in the case of low serum insulin concentrations and elevated levels of big IGF2. Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels.
Learning points
-
NICTH is a very rare condition that should be considered in patients known to have mesenchymal or malignant epithelial tumors and suffering from recurrent episodes of hypoglycemia.
-
The diagnosis of an NICTH is established on the basis of the hypoinsulinemic hypoglycemia, the MSFT history, and the presence of paraneoplastic secretion of IGF1 or an immature form of IGF2.
-
Treatment with corticosteroids, GH, or both can improve hypoglycemic symptoms and restore plasma glucose to normal levels in NICTH.
