An Interesting Cause of Hyperhidrosis and Hyperphagia - Acromegaly


Dr Mohamed Iliyas, Dr Sundaramurthy    20 November 2017


Acromegaly, Gigantism, Pituitary macroadenoma, Growth hormone, Insulin like growth factor, Macroglossia


Acromegaly is a rare disease with an annual incidence of 3-4 cases/1 million due to hypersecretion of growth hormone from a pituitary tumour or an extrapituitary tumour like lymphoma or pancreatic islet cell tumour. Less commonly it can be due to growth hormone releasing hormone (GHRH) secreting tumours, usually carcinoids or small cell lung cancer. Pituitary adenomas are the most common cause of acromegaly. When the lesion is a pituitary GH - secreting somatotroph adenoma, acromegaly features are present. If the lesion is an acidophil stem cell adenoma secreting GH and Prolactin, hyperprolactinemia features predominate and is frequently encountered in teenagers often causing gigantism (3). If the culprit lesion is a mixed mammosomatotroph tumour, both the features are present. GH cell carcinomas are very rare and should be suspected when extracranial metastases are present. Carcinoids are the most common cause of acromegaly due to GHRH secreting tumours. Multiple endocrine neoplasia-1, Familial acromegaly, Carney’s syndrome and McCune-Albright syndrome are the familial syndromes causing acromegaly.


A 34 year old male attended our Medical outpatient department with complains of excessive sweating and increased appetite since 6 months. There was a history of excessive sleeping, easy fatigability, holocranial headache, increased frequency of micturition around 4 times in the night & breathlessness progressing from NYHA Grade I to II. These symptoms started appearing one by one during the last 6 months. He noticed that his hands have become broad but attributed it to heavy work that he does. His shirt size had changed from 40 to 44 inches, footwear from 10 to 12 inches and brief from 90 to 100 cm. His wife complained that his voice has become hoarse since 5 months. There was no history of visual disturbance, vomiting, chest pain, leg swelling or change in personality. His sexual life is normal. He had a road traffic accident 3 years back. There was contusion of right hypothalamus with intraventricular haemorrhage for which drainage was done. Splenectomy was done for splenic injury and hemoperitoneum.

On general examination he had coarse facies, high arched palate, macroglossia, prognathism, spade like fingers and broad feet. His vitals were BP-130/90 mmHg, Pulse rate 80/minute, Respiratory rate 14/minute. His systemic examination was normal. Eye examination was done by ophthalmologists. Both eyes had congested bulbar conjunctiva, chemosis, proptosis, restricted abduction and adduction with normal fundus, colour vision, field of vision. There was no diplopia on diplopia charting. Hematological investigations revealed dimorphic anemia (Hb-6.8 g/dl) with thrombocytosis (8.17 lakh/cubic mm). Renal and Liver function tests were normal. Serum IGF-1 level was elevated 841ng/ml (Normal: 115-307). Serum Prolactin was mildly elevated 18.65 ng/ml (Normal: 2.1-17.7). CT brain was normal. 1.5 Tesla MRI brain with contrast showed a well-defined oval shaped mass of size 2 × 1.6 cm lesion in the sellar region. It was isointense on T1 and hypointense on T2 images with heterogeneous enhancement post contrast. The lesion did not extend to suprasellar region or involve optic chiasma. These features were suggestive of pituitary macro adenoma.

Screening of other organs were done since Acromegaly affects almost all organs. Echocardiography showed concentric left ventricular hypertrophy with normal ejection fraction (60%). Ultrasound (USG) of the abdomen showed Left grade IV Hydroureteronephrosis. CT abdomen showed Left Pelviuretericjunction obstruction with gross Hydroureteronephrosis. We suspected prior renal calculi. But his serum calcium (ionised-4.2 mg/dl) & intact Parathyroid hormone (37.97 pg/ml) were normal. USG of the neck showed diffuse nodular goitre confirmed by FNAC. Thyroid function test was normal (FT3 - 3.36pg/ml, FT4 - 1.20ng/ml, TSH - 1.16 microIU/ml). Multiple endocrine neoplasia was ruled out by the above investigations.

Tablet Cabergoline 0.5mg twice a week was started as per endocrine surgeon’s advice. 2 units of packed RBCs were transfused. Team of endocrine and skull base surgeons resected the tumour by trans-nasal trans-sphenoidal endoscopic approach. Histopathological examination showed fairly uniform round to oval cells with eosinophilic cytoplasm and centrally placed darkly staining nucleus arranged in cords, sheets and islands. Focal areas of rosette formation and separation of tumour cells by fibrovascular septae was present. These features confirmed the lesion as pituitary adenoma. Post operatively his IGF1 & GH levels decreased. He was discharged and is on regular follow up.


GH secretion is increased by GHRH, ghrelin, fasting whereas somatostatin and food intake suppresses its release. The effects of GH are mediated through GH receptors in the cartilages and liver. GH leads to Insulin like growth factor-1 (IGF-1). IGF1 are highest during late adulthood and in pregnancy. IGF1 production is decreased in patients with hypothyroidism, hepatic disease, poorly controlled diabetes and in malnourished patients (4). IGF1 & GH act dependently & independently to cause the features of hypersomatotropism. Acromegalics have characteristic features like coarse facies, frontal bossing, large fleshy lips and nose, macroglossia, prognathism, increased gap between lower incisors, spade like fingers.

At the time of diagnosis around 60% of the patients have hypertension, arrhythmia and valvular heart diseases which causes concentric ventricular hypertrophy and diastolic heart failure(4). Our patient had concentric hypertrophy but didn’t progress to heart failure at the time of diagnosis. Heart failure is reversible with octreotide treatment while hypertension, and valvular regurgitation are not (4). Resting ECG can show ST segment depression, T wave abnormalities, conduction defects and arrhythmias in 50% of patients. Colon cancer risk is twice common than the general population hence screening by colonoscopy once in 3 to 5 years is advised (5). Our patient was not cooperative for the procedure, however stool occult blood was negative. Obstructive sleep apnea, snoring and narcolepsy due to soft tissue deposition around the larynx, macroglossia and nasal polyps are present in more than 50% patients (6). Central sleep apnea associated with high GH & IGF1 leves is also common. Voice changes is also common due to the fixation of vocal cords, laryngeal stenosis, tracheal calcification and cricoarytenoid joint arthropathy. Our patient had a deep voice, snoring and macroglossia.

Musculoskeletal manifestations are the most common features in acromegaly. Upto70% patients have arthropathy in the form of joint swelling, hypermobility and cartilage thickening. Knee, elbow, shoulder, ankle hip and lumbosacral joints are commonly affected. Kyphoscoliosis is common. Our patient had kyphosis. Carpal tunnel syndrome is seen in half of patients due to median nerve enlargement and its entrapment in the wrist. Osteophytes are commonly seen in the anterior aspects of vertebrae and in the phalangeal tufts mainly the distal phalanges giving an appearance of spade like fingers on xray. Hyperhidrosis and malodorous oily skin is present in 70% of patients and is an early sign. Our patient sought medical attention for this which helped us diagnose the pituitary lesion.

Increased glycosaminoglycan deposition and collagen production causes the typical coarse facies with skin wrinkles, nasolabial folds, fleshy nose, macroglossia, increased heel pad thickness. Heel pad thickness is measured in x-ray of the foot in a lateral view. The distance is measured between the lower most point of the calcaneum and the lower most point of the heel pad soft tissue shadow. If the measurement is >23mm in males and >21mm in females, the heel pad thickness is said to be increased. Phenytoin therapy, obesity and myxedema can also cause heel pad thickening. Exophthalmos if present is frequently masked by frontal bossing. Skin tags if more than 3 in number in patients above 50 years of age is a marker of colonic adenomatous polyps not related to the GH & IGF1 levels.

Impaired glucose tolerance and Diabetes mellitus is very common because of the anti-insulin effects of GH. This is reversed after surgery or somatostatin analogue therapy. Our patient was euglycemic. 30% of patients have coexisting hyperprolactinemia. Our patient had mildly elevated prolactin. Hypogonadism is present in 50% of patients which is often reversible. Thyroid dysfunction is quite common and may present with grave’s disease, nodular or diffuse goitre, toxic or nontoxic goitre. Our patient had diffuse goitre with normal thyroid function test. Screening for MEN1 syndrome was done but parathyroid hormone was within normal levels. Age, level of GH before and after treatment, IGF1 levels, size of the tumour, degree of invasion and duration of symptoms before the diagnosis is made are important determinants of coexisting illnesses (4). Some important mortality determinants are high IGF1 levels, GH level >2.5 microgram/litre, older age, cardiac disease, hypertension, inadequately replaced ACTH dependent adrenal insufficiency and history of pituitary radiation (7). Younger age, shorter duration of the disease, GH levels <2.5 microgram/litre, absence of hypertension independently predict longer survival (8).

The single best test to diagnose acromegaly is age and sex matched serum IGF1 level. It is elevated in all patients with acromegaly distinguishing it from normal individuals (9). Our patient had a very high level of IGF1. GH is secreted in a phasic manner in normal individuals with the lowest levels during the day often <2 microgram/litre, while in the night it can be as high as 30 microgram/litre (10). GH level is also influenced by sleep and food intake with a very short half-life (20 minutes). Hence serum IGF1 levels are preferred over GH levels. However in patients with equivocal IGF1 levels, measurement of GH levels is additive. Oral Glucose Tolerance Test (OGTT) is the most specific dynamic test. It is also the gold standard test to determine control of GH secretion post surgery. OGTT is done by measurement of GH levels over 2 hours of ingestion of 75g of glucose. GH levels ≥ 0.4 microgram/litre in OGTT is diagnostic of acromegaly. GH <1 microgram/litre signifies disease control. MRI brain with contrast is the radiological investigation of choice. Information on size of the tumour along with compression and invasion of adjacent structures can be obtained. Even a tumour of 2mm can be identified but it doesn’t differentiate functioning and non-functioning tumours. Macroadenoma (>1cm) is seen in 75% patients. Other endocrine glands should be imaged as a part of routine workup. ACROSCORE is a clinical tool developed for general practitioners and non-endocrinology specialists for easier identification of acromegaly. It classifies the patient into low, medium or high risk of suspicion of acromegaly.

Surgical resection is the 1st management option for all acromegalics (11). The transphenoidal approach normalises IGF1 & GH in >80% microadenomas and <50% macroadenomas. Recurrence or persistence of tumour is 6% in this approach. Conventional radiotherapy & stereotactic radiosurgery causes hypopituitarism in >50% while normalising IGF1 & GH in only 30%. The somatostatin analogues (Octreotide, lanreotide) shrinks the tumour by 50% and normalising IGF1 & GH in 70% of patients. The GH receptor antagonist Pegvisomant normalises IGF1 in >90% patients (4). Currently this drug is preferred when other treatment modalities have failed, very high levels of IGF1 (>900ng/ml) or whose glucose tolerance is worsened by somatostatin analogues (11). The dopamine agonist Cabergoline is less commonly used nowadays because <15% normalisation of IGF1 & GH.




  1. Kauppinen-Makelin R, Sane T, Reunanen A, et al. A nationwide survey of mortality in acromegaly. J Clin  Endocrinol Metab 2005;90:4081-6.
  2. Jagdresic A, Banks LM, Child DF, et al. The acromegaly syndrome: relation between clinical features,  growth hormone values and radiological characteristics of the pituitary tumours. Q J Med. 1982;51:189-204
  3. Maheshwari HG, Prezant TR, Herman-Bonert V, et al. Long-acting peptidomimergic control of gigantism  caused by pituitary acidophilic stem cell adenoma. J Clin Endocrinol Metab 2000;85:3409-16
  4. Melmed S (2006) Medical progress. Acromegaly N Engl J Med 355(24):2558–2573.
  5. Renehan AG, Shalet SM. Acromegaly and colorectal cancer: risk assessment should be based on  population-based studies. J Clin Endocrinol Metab 2002;87:1909.
  6. Rosenow F, Reuter S, Deuss U, et al. Sleep apnoea in treated acromegaly: relative frequency and  predisposing factors. Clin Endocrinol (Oxf) 1996;45:563-9.
  7. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary  radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in  patients with acromegaly. J Clin Endocrinol Metab 2004;89:1613-7.
  8. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 2004; 89:667-74.
  9. Stofel-Wagner B, Springer W, Bidlingmaier F, Klingmuller D. A comparison of different methods of diagnosing acromegaly. Clin endicrinol (Oxf) 1997; 46:531.
  10. Peacey SR, Toogood AA, Veldhuis JD, Thorner MO, Shalet SM. The relationship between 24-hour growth hormone secretion and insulin-like growth factor I in patients with successfully treated  acromegaly: impact of surgery or radiotherapy. J Clin Endocrinol Metab 2001;86:259-66.
  11. American Association Of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly. endocrine practice vol 10 no. 3 may/june 2004.

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