Clinical Overview > Topic > Pituitary
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Summary
Acromegaly is a rare, chronic progressive disorder with characteristic clinical features caused by persistent hypersecretion of growth hormone (GH), mostly from a pituitary adenoma (95%). Occasionally, ectopic production of GH or growth hormone-releasing hormone (GHRH) with resultant GH hypersecretion may lead to acromegaly. Sometimes localizing the source of GH hypersecretion may prove difficult. Rarely, acromegaly has been found in patients with an empty sella (ES) secondary to prior pituitary radiation and/or surgery. However, acromegaly in patients with primary empty sella (PES) is exceeding rarely and has only been described in a few cases. We describe a 47-year-old male who presented with overt features of acromegaly (macroglossia, prognathism, increased hand and feet size). Biochemically, both the serum GH (21.6 μg/L) and insulin-like growth factor 1 (635 μg/L) were elevated. In addition, there was a paradoxical elevation of GH following a 75 g oral glucose load. Pituitary MRI demonstrated an ES. In order to exclude an ectopic source of GH hypersecretion, further biochemical tests and imaging were done, which were unremarkable. Notably, increased uptake in the sella turcica on the 68Gallium DOTATATE PET/CT confirmed the ES as the likely source of GH secretion. As no overt lesion was noted, medical treatment (octreotide acetate) was initiated with a good clinical and biochemical response. At his 3 month follow-up, he reported an improvement in symptoms (fatigue and headache), however he still complained of low libido. Due to a persistently low testosterone level at follow-up, a long-acting testosterone was initiated. His GH level normalised, and IGF-1 has significantly reduced.
Learning points
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The commonest cause of acromegaly is due to GH hypersecretion from pituitary adenomas (95%).
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Acromegaly has rarely been found in patients with ES.
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It is important to exclude a past history suggestive of pituitary apoplexy.
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Extra-pituitary source of GH such as ectopic production of GHRH with resultant GH hypersecretion needs to be excluded.
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In such cases, since there is no resectable mass, medical therapy is the primary treatment option.
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Division of Clinical Nutrition and Metabolism, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
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Summary
IgG4-related hypophysitis is an autoimmune hypophysitis associated with IgG4-related disease. Swelling of the pituitary gland is responsive to steroid therapy, but the prognosis of pituitary function after the treatment remains unclear. The present case implies that transiently improved pituitary function can re-worsen during long-term follow-up in IgG4-related hypophysitis. A 71-year-old male patient with IgG4-related hypophysitis visited a nearby hospital with malaise, anorexia, and polyuria. Pituitary dysfunction was suspected, so he was referred to our hospital for further examination. Imaging studies and laboratory data showed swelling of the pituitary gland and panhypopituitarism, which dramatically improved following steroid therapy. There was no evidence of relapsing IgG4-related disease during prednisolone tapering. Pituitary function was examined after 4 years under treatment with low-dose prednisolone; surprisingly, anterior pituitary function had worsened again. Our case suggests a need for continuous monitoring of pituitary function after steroid therapy for IgG4-related hypophysitis. This report illustrates the natural course of pituitary function in IgG4-related hypophysitis and may be informative when considering the introduction of steroid therapy.
Learning points
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Steroid therapy is an effective first-line therapy for pituitary dysfunction and pituitary swelling in IgG4-related hypophysitis.
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Pituitary function can worsen again during follow-up, despite transient improvement after steroid therapy in IgG4-related hypophysitis.
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Continuous monitoring of pituitary function is necessary for IgG4-related hypophysitis, regardless of disease activity.
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Faculty of Health and Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, University of Queensland, Queensland, Australia
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Summary
Although pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) are also extremely rare. Here we report the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. Biochemical assessment confirmed acromegaly. Following trans-sphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour.
Learning points
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Pituitary tumours most commonly present with symptoms related to endocrine disturbance or mass effects upon visual pathways (e.g. optic chiasm, nerves in the lateral cavernous sinus). However, extremely rarely, pituitary masses may disrupt cerebrospinal fluid (CSF) circulation resulting in hydrocephalus.
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Sellar gangliocytomas are very rare tumours and most of them are hybrid tumours with pituitary adenomas (SGPAs).
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SGPAs are typically indolent and may be functioning or non-functioning tumours.
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Growth hormone (GH)-producing SGPAs are less likely to respond to somatostatin agonists than classic somatotrophinomas.
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Primary surgical debulking via a trans-sphenoidal approach was effective in this individual, leading to the restoration of CSF circulation and improvement in visual disturbance, while also negating the need for permanent CSF diversion despite the residual tumour burden.
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Summary
A 61-year-old man developed central diabetes insipidus caused by mixed histiocytosis (MH) representing Langerhans cell histiocytosis overlapping with Erdheim–Chester disease. Bone, skin, vascular, and retroperitoneal involvements were also observed. Dynamic hormonal testing showed normal responses for anterior pituitary hormones, except for impaired secretion of growth hormone (GH). MRI of the brain showed thickening of the pituitary stalk with slightly reduced signal hyperintensity in the posterior pituitary lobe on T1-weighted imaging. During 2 years of follow-up without radical treatment for MH, imaging studies suggested extension of vascular and retroperitoneal involvements. In contrast, brain MRI did not show any particular interval changes, except for the disappearance of hyperintense signalling in the posterior pituitary lobe. Moreover, no other anterior pituitary dysfunctions beyond GH deficiency emerged during the 2 years of follow-up. The natural history of MH in this case is described, focusing on serial assessments of pituitary functions using dynamic tests.
Learning points
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Erdheim–Chester disease and Langerhans cell histiocytosis overlapping as MH was described, focusing on pituitary functions.
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MH caused both GH deficiency and central diabetes insipidus.
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Despite a lack of radical therapy for MH, no other anterior pituitary dysfunctions emerged for 2 years.
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Radiological images showed no particular interval changes in pituitary stalk lesions, while vascular and retroperitoneal involvements extended.
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Summary
Acromegaly is associated with a low quality of life (QoL), which is partially attributable to appearance. However, appearance changes are only partially reversible with treatments of growth hormone excess. This case study describes a 41-year-old Japanese man who presented with mandibular prognathism. Acromegaly was suspected because of the patient’s facial features. Subsequent examination revealed a pituitary tumour with elevated levels of growth hormone and insulin-like growth factor 1 (IGF1), confirming a diagnosis of acromegaly. We assessed his QoL with the acromegaly QoL questionnaire (AcroQoL) before transsphenoidal surgery, and all AcroQoL scores were low. Although the pituitary adenoma was resected, his serum IGF1 levels started to increase again and MRI identified a residual pituitary lesion. After lanreotide and pegvisomant injection therapies improved his serum IGF1 levels, we reassessed his AcroQoL scores, however, the results showed worsening scores regarding appearance and personal relationships, and the patient expressed interest in surgery for mandibular prognathism. We performed sagittal split ramus osteotomy (SSRO) with Le Fort I osteotomy, thus, the patient’s AcroQoL scores improved. This case shows that SSRO with Le Fort I osteotomy for mandibular prognathism, rather than control of serum IGF1 level alone, improved the patient’s AcroQoL score, especially for both psychological well-being and approval of appearance. Acromegaly has many complications, including its negative impact on patients’ perception of their appearance and patients’ QoL can be improved using multiple options, in addition to controlling growth hormone levels.
Learning points
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The patient’s AcroQoL scores worsened despite biochemical normalization of IGF-1 levels.
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Mandibular prognathism due to acromegaly can be successfully operated by performing sagittal split ramus osteotomy with Le Fort I osteotomy.
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Frequent monitoring of AcroQoL scores and appropriate response to negative results can improve the overall QoL.
Kilimanjaro Christian Medical University College, Moshi, Tanzania
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Kilimanjaro Christian Medical University College, Moshi, Tanzania
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Department of Radiology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
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Kilimanjaro Christian Medical University College, Moshi, Tanzania
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Summary
Acromegaly is a rare disease caused by hypersecretion of the growth hormone (GH). Most cases are caused by either pituitary microadenoma or macroadenoma. The GH producing tumors present with clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumor. The physical changes are usually slow and, therefore, recognition of the disease is delayed. These adenomas are never malignant but can have significant morbidity and mortality. A subgroup of patients with acromegaly present with severe hyperglycemia resulting in diabetic ketoacidosis (DKA) which requires insulin. Rarely are pituitary tumors responsible for generalized convulsions except when they are too large. We hereby present two cases, the first is that of a 26-year-old female who presented with new onset status epilepticus, DKA with a 1-year history of diabetes mellitus (DM). On examination, she had clinical features of acromegaly. The second case is that of a 34-year-old female who presented with new onset status epilepticus, hyperglycemia with a history of recently diagnosed DM, and features of gigantism. In both cases, their diagnosis was confirmed by elevated serum GH and later by elevated insulin-like growth factor type 1 levels, and CT of the head demonstrating large pituitary macroadenoma. The importance of clinical history and examination, as well as investigations is vital in the recognition of acromegaly. The prognosis of acromegalic patients depends on early clinical recognition and tumor size reduction by either medical or surgical therapy.
Learning points
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Conditions such as status epilepticus and DKA may be clinical presentations in patients presenting with acromegaly.
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Seizures are rare in people with pituitary adenoma and typically occur when the tumor invades the suprasellar area due to mass effect on the brain.
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This article shows how best we were able to manage the acromegaly complications in a low resource setting.
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Hyperprolactinemia in acromegaly may be due to disruption of the normal dopaminergic inhibition of prolactin secretion due to mass effect of the macroadenoma, and around 25% of GH-secreting adenomas co-secrete prolactin.
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Summary
Hypoglycemia is an uncommon clinical problem in non-diabetic patients or patients not being treated for diabetes mellitus. It is a rare, but well-established complication of bariatric surgery and, in some cases, it can be the only symptom of another medical problem. A 50-year-old woman with a history of partially recovered hypopituitarism after transsphenoidal surgery for a non-functioning pituitary macroadenoma complained about symptomatic hypoglycemia after sleeve gastrectomy surgery. Our initial studies failed to determine the cause for these episodes and treatment with acarbose (suspecting a dumping syndrome) was not helpful. Finally, laboratory findings revealed growth hormone (GH) deficiency. The patient received treatment with GH, with the resolution of symptoms after 3 months of treatment. Our case suggests that all causes of hypoglycemia should be considered and studied after bariatric surgery. An improvement in insulin-resistance following bariatric surgery can trigger clinical manifestations of GH deficiency.
Learning points:
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Postprandial hypoglycemia after bariatric surgery is usually due to dumping syndrome.
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Even after bariatric surgery, all causes of hypoglycemia should be considered and studied.
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After significant weight loss, insulin sensitivity is usually restored and can trigger clinical manifestations of GH deficiency.
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Hypoglycemia is a rare symptom of GH deficiency.
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Summary
Thyroid stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is an uncommon cause of thyrotoxicosis, and is even rarer when found during pregnancy. Our patient presented with thyrotoxicosis accompanied by an inappropriately normal TSH level at 10 weeks of gestation during work-up of surgical termination of pregnancy (STOP). Subsequent investigations performed after STOP confirmed the presence of a TSH-secreting pituitary macroadenoma. She was initially treated with anti-thyroid drugs for biochemical control, followed by trans-sphenoidal surgery after STOP had been performed. Her thyroid function completely normalized after the trans-sphenoidal surgery. Our case illustrated the importance of recognizing the syndrome of inappropriate TSH secretion and highlighted several pregnancy-related aspects in the diagnosis and management of TSHoma during pregnancy.
Learning points:
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This case report illustrates the need to raise awareness in recognizing the syndrome of inappropriate TSH secretion.
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Illustrate the different hormone tests available for reaching the diagnosis of TSH-secreting pituitary adenoma.
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Highlight the physiological changes in the thyroid status during pregnancy and the importance of using trimester-specific reference ranges for assessment of thyroid function during pregnancy.
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Describe the challenges in the management of TSH-secreting pituitary adenoma during pregnancy.
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Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal
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Faculty of Medicine, Porto University, Porto, Portugal
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Summary
Pituitary metastasis (PM) can be the initial presentation of an otherwise unknown malignancy. As PM has no clinical or radiological pathognomonic features, diagnosis is challenging. The authors describe the case of a symptomatic PM that revealed a primary lung adenocarcinoma. A 62-year-old woman with multiple sclerosis and no history of malignancy, incidentally presented with a diffusely enlarged and homogeneously enhancing pituitary gland associated with stalk enlargement. Clinical and biochemical evaluation revealed anterior hypopituitarism and diabetes insipidus. Hypophysitis was considered the most likely diagnosis. However, rapid visual deterioration and pituitary growth raised the suspicion of metastatic involvement. A search for systemic malignancy was performed, and CT revealed a lung mass, which proved to be a lung adenocarcinoma. Accordingly, the patient was started on immunotherapy. Resection of the pituitary lesion was performed, and histopathology analysis revealed metastatic lung adenocarcinoma. Following surgery, the patient underwent radiotherapy. More than 2 years after PM detection, the patient shows a clinically relevant response to antineoplastic therapy and no evidence of PM recurrence.
Learning points:
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Although rare, metastatic involvement of the pituitary gland has been reported with increasing frequency during the last decades.
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Pituitary metastasis can be the initial presentation of an otherwise unknown malignancy and should be considered in the differential diagnosis of pituitary lesions, irrespective of a history of malignancy.
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The sudden onset and rapid progression of visual or endocrine dysfunction from a pituitary lesion should strongly raise the suspicion of metastatic disease.
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MRI features of pituitary metastasis can overlap with those of other pituitary lesions, including hypophysitis; however, rapid pituitary growth is highly suggestive of metastatic disease.
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Survival after pituitary metastasis detection has improved over time, encouraging individualized interventions directed to metastasis to improve quality of life and increase survival.
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Summary
An 11-year-old girl presented with acute lower limb weakness, dehydration, hypernatraemia and secondary rhabdomyolysis on a background of an 8-month history of polyuria. Radiological investigations revealed a suprasellar tumour which was diagnosed on biopsy as a non-metastatic germinoma. Further endocrinological investigations confirmed panhypopituitarism and she commenced desmopressin, hydrocortisone and thyroxine. Her chemotherapeutic regime consisted of etoposide, carboplatin and ifosfamide, the latter of which required 4 litres of hyperhydration therapy daily. During the first course of ifosfamide, titration of oral desmopressin was trialled but this resulted in erratic sodium control leading to disorientation. Based on limited literature, we then trialled an arginine-vasopressin (AVP) infusion. A sliding scale was developed to adjust the AVP dose, with an aim to achieve a urine output of 3–4 mL/kg/h. During the second course of ifosamide, AVP infusion was commenced at the outset and tighter control of urine output and sodium levels was achieved. In conclusion, we found that an AVP infusion during hyperhydration therapy was required to achieve eunatraemia in a patient with cranial diabetes insipidus. Developing an AVP sliding scale requires individual variation; further reports/case series are required to underpin practice.
Learning points:
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Certain chemotherapeutic regimens require large fluid volumes of hyperhydration therapy which can result in significant complications secondary to rapid serum sodium shifts in patients with diabetes insipidus.
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The use of a continuous AVP infusion and titrating with a sliding scale is more effective than oral desmopressin in regulating plasma sodium and fluid balance during hyperhydration therapy.
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No adverse effects were found in our patient using a continuous AVP infusion.
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Adjustment of the AVP infusion rate depends on urine output, fluid balance, plasma sodium levels and sensitivity/response of the child to titrated AVP doses.