Diagnosis and Treatment > Medication
Search for other papers by Mariana Barbosa in
Google Scholar
PubMed
Search for other papers by Sílvia Paredes in
Google Scholar
PubMed
Search for other papers by Maria João Machado in
Google Scholar
PubMed
Pituitary Consult, Hospital de Braga, Braga, Portugal
Search for other papers by Rui Almeida in
Google Scholar
PubMed
Pituitary Consult, Hospital de Braga, Braga, Portugal
Search for other papers by Olinda Marques in
Google Scholar
PubMed
Summary
Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment.
Learning points:
-
Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer.
-
This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma.
-
PA presents with classic clinical signs and symptoms that should be promptly recognized.
-
Patients should be instructed to seek medical care if suspicious symptoms occur.
-
Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.
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 H Joshi in
Google Scholar
PubMed
Search for other papers by M Hikmat in
Google Scholar
PubMed
Search for other papers by A P Devadass in
Google Scholar
PubMed
Search for other papers by S O Oyibo in
Google Scholar
PubMed
Search for other papers by S V Sagi in
Google Scholar
PubMed
Summary
IgG4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory condition which can affect various organs including the pituitary gland. The true annual incidence of this condition remains widely unknown. In addition, it is unclear whether IgG4 antibodies are causative or the end result of a trigger. With no specific biomarkers available, the diagnosis of IgG4-related hypophysitis remains a challenge. Additionally, there is a wide differential diagnosis. We report a case of biopsy-proven IgG4-related hypophysitis in a young man with type 2 diabetes mellitus.
Learning points:
-
IgG4-related hypophysitis is part of a spectrum of IgG4-related diseases.
-
Clinical manifestations result from anterior pituitary hormone deficiencies with or without diabetes insipidus, which can be temporary or permanent.
-
A combination of clinical, radiological, serological and histological evidence with careful interpretation is required to make the diagnosis.
-
Tissue biopsy remains the gold standard investigation.
-
Disease monitoring and long-term management of this condition is a challenge as relapses occur frequently.
Search for other papers by Raluca Maria Furnica in
Google Scholar
PubMed
Search for other papers by Julie Lelotte in
Google Scholar
PubMed
Search for other papers by Thierry Duprez in
Google Scholar
PubMed
Search for other papers by Dominique Maiter in
Google Scholar
PubMed
Search for other papers by Orsalia Alexopoulou in
Google Scholar
PubMed
Summary
A 26-year-old woman presented with severe postpartum headaches. Magnetic resonance imaging (MRI) revealed a symmetric, heterogeneous enlargement of the pituitary gland. Three months later, she developed central diabetes insipidus. A diagnosis of postpartum hypophysitis was suspected and corticosteroids were prescribed. Six months later, the pituitary mass showed further enlargement and characteristics of a necrotic abscess with a peripheral shell and infiltration of the hypothalamus. Transsphenoidal surgery was performed, disclosing a pus-filled cavity which was drained. No bacterial growth was observed, except a single positive blood culture for Staphylococcus aureus, considered at that time as a potential contaminant. A short antibiotic course was, however, administered together with hormonal substitution for panhypopituitarism. Four months after her discharge, severe headaches recurred. Pituitary MRI was suggestive of a persistent inflammatory mass of the sellar region. She underwent a new transsphenoidal resection of a residual abscess. At that time, the sellar aspiration fluid was positive for Staphylococcus aureus and she was treated with antibiotics for 6 weeks, after which she had complete resolution of her infection. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.
Learning points:
-
The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.
-
In a significant proportion of cases no pathogenic organism can be isolated.
-
A close follow-up is necessary given the risk of recurrence and the high rate of postoperative pituitary deficiencies.
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Search for other papers by Nikolaos Asonitis in
Google Scholar
PubMed
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
Search for other papers by Eva Kassi in
Google Scholar
PubMed
Search for other papers by Michalis Kokkinos in
Google Scholar
PubMed
Search for other papers by Ilias Giovanopoulos in
Google Scholar
PubMed
Search for other papers by Foteini Petychaki in
Google Scholar
PubMed
Search for other papers by Helen Gogas in
Google Scholar
PubMed
Summary
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.
Learning points:
-
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.
-
Breast cancer has the highest prevalence of hypercalcemia.
-
The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).
-
In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.
Search for other papers by Andromachi Vryonidou in
Google Scholar
PubMed
Search for other papers by Stavroula A Paschou in
Google Scholar
PubMed
Search for other papers by Fotini Dimitropoulou in
Google Scholar
PubMed
Search for other papers by Panagiotis Anagnostis in
Google Scholar
PubMed
Search for other papers by Vasiliki Tzavara in
Google Scholar
PubMed
Search for other papers by Apostolos Katsivas in
Google Scholar
PubMed
Summary
We describe a case of a 40-year-old woman who was admitted to the intensive care unit with a rapid onset of dyspnea and orthopnea. She presented progressive weakness, weight loss and secondary amenorrhea during last year, while intermittent fever was present for the last two months. Initial biochemical evaluation showed anemia, hyponatremia and increased C-reactive protein levels. Clinical and echocardiographic evaluation revealed cardiac tamponade, which was treated with pericardiocentesis. Pleural fluid samples were negative for malignancy, tuberculosis or bacterial infection. Hormonal and serologic evaluation led to the diagnosis of autoimmune polyglandular syndrome (APS) type 2 (including primary adrenal insufficiency and autoimmune thyroiditis), possibly coexisting with systemic lupus erythematosus. After symptomatic rheumatologic treatment followed by replacement therapy with hydrocortisone and fludrocortisone, the patient fully recovered. In patients with the combination of polyserositis, cardiac tamponade and persistent hyponatremia, possible coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal insufficiency, should be considered. Early diagnosis and non-invasive treatment can be life-saving.
Learning points:
-
In patients with the combination of polyserositis, cardiac tamponade and persistent hyponatremia, possible coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal insufficiency, should be considered.
-
Early diagnosis and non-invasive treatment can be life-saving for these patients.
-
Primary adrenal insufficiency requires lifelong replacement therapy with oral administration of 15–25 mg hydrocortisone in split doses and 50–200 µg fludrocortisone once daily.
Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany
Search for other papers by Anna Kopczak in
Google Scholar
PubMed
Search for other papers by Adrian-Minh Schumacher in
Google Scholar
PubMed
Search for other papers by Sandra Nischwitz in
Google Scholar
PubMed
Search for other papers by Tania Kümpfel in
Google Scholar
PubMed
Search for other papers by Günter K Stalla in
Google Scholar
PubMed
Search for other papers by Matthias K Auer in
Google Scholar
PubMed
Summary
The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE) gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD) antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS). The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE) was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.
Learning points:
-
Episodic nausea cannot only be a sign of Addison’s disease, but can also be caused by epileptic seizures with gastrointestinal aura due to limbic encephalitis.
-
GAD antibodies are not only found in diabetes mellitus type 1, but they are also associated with autoimmune limbic encephalitis and can appear over time.
-
Limbic encephalitis can be another manifestation of autoimmune disease in patients with APECED/APS-1 that presents over the time course of the disease.
Search for other papers by Catarina Roque in
Google Scholar
PubMed
Search for other papers by Ricardo Fonseca in
Google Scholar
PubMed
Search for other papers by Carlos Tavares Bello in
Google Scholar
PubMed
Search for other papers by Carlos Vasconcelos in
Google Scholar
PubMed
Search for other papers by António Galzerano in
Google Scholar
PubMed
Search for other papers by Sância Ramos in
Google Scholar
PubMed
Summary
Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma.
Learning points:
-
Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.
-
Hyperpigmentation is frequently absent.
-
The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.
-
Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.
-
In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.
-
High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.
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.
