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ORIGINAL ARTICLE
Year : 2008  |  Volume : 54  |  Issue : 2  |  Page : 110-114

Characterization of adult onset growth hormone deficiency syndrome in patients with hypothalamopituitary diseases: Asian Indian data


Department of Endocrinology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai, India

Correspondence Address:
T R Bandgar
Department of Endocrinology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.40777

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 :: Abstract 

Background: Hardly any data is available on Adult onset growth hormone deficiency (AOGHD) in Patients with hypothalamopituitary diseases in India. Aims: To characterize Asian Indian AOGHD syndrome in hypothalamopituitary diseases. Settings and Design: Cross-sectional analysis of data from a tertiary care hospital. Materials and Methods: Thirty patients with AOGHD were compared with 30 age-, sex-, body mass index-matched controls with respect to endocrine evaluation, biochemistry, body composition (BC), bone mineral density (BMD), cardiovascular risk profile and quality of life (QoL). Statistical Analysis Used: Comparisons were performed using two-tailed Student's test (SPSS Software version 10.0). Results: Most of the patients had abnormal BC with central obesity [Truncal FM (%): males {33.9±4.4 (patient) vs. 29.31±6.2 (control); P -0.027}; females {39.87±5.93 (patient) vs. 35.76±3.16 (control); P - 0.025}] and poor QoL. Patients aged over 45 years did not show low bone mass or lipid abnormalities as compared to controls. Low BMD and abnormal lipid profile {Triglycerides [mg/dl]:170.55±72.5 (patient) vs101.24±31.0 (control); P -0.038}; {very low density lipoprotein cholesterol [mg/dl]: 33.54±14.9 (patient) vs. 20.25±6.18 (control); P - 0.05} was seen in female patients less than 45 years of age. Conclusions: Male and female (more than 45 years) AOGHD patients have increased cardiovascular risk factors and poor QoL while BMD is unaffected. Females less than 45 years of age have the major characteristics of AOGHD and would be the group to benefit maximally with recombinant human Growth Hormone treatment, which is similar to that in the western literature.


Keywords: Adult onset growth hormone deficiency syndrome, Asian Indian data, hypothalamopituitary diseases


How to cite this article:
Bandgar T R, Prashanth M, Joshi S R, Menon P S, Shah N S. Characterization of adult onset growth hormone deficiency syndrome in patients with hypothalamopituitary diseases: Asian Indian data. J Postgrad Med 2008;54:110-4

How to cite this URL:
Bandgar T R, Prashanth M, Joshi S R, Menon P S, Shah N S. Characterization of adult onset growth hormone deficiency syndrome in patients with hypothalamopituitary diseases: Asian Indian data. J Postgrad Med [serial online] 2008 [cited 2020 Jul 2];54:110-4. Available from: http://www.jpgmonline.com/text.asp?2008/54/2/110/40777


Adult onset growth hormone deficiency syndrome (AOGHD) occurs in patients with a known pituitary pathology or in those who have previously received full conventional pituitary hormone replacement therapy. [1] The AOGHD patients have abnormal body composition (BC) with reduced lean body mass, increased fat mass, reduced strength and exercise capacity, impaired psychological wellbeing, reduced bone mineral density (BMD) and increased cardiovascular risk factors. With Growth Hormone (GH) treatment there is normalization of the above parameters. [2],[3] The present study was undertaken to characterize the AOGHD syndrome in patients with hypothalamopituitary diseases in a tertiary institute in Mumbai, as there is no published Indian data on this subject till date.


 :: Materials and Methods Top


Thirty-four patients (aged 33-60 years) with suspected AOGHD attending Endocrine Clinic from 2001-2004,who were on replacement doses for hormonal deficiencies (except growth hormone) for at least six months before entry into the study were evaluated prospectively after obtaining informed consent. The study was approved by the local ethics committee. Patients with malignant lesion, secretory pituitary tumors or other systemic disorders were excluded. The subjects included those who had undergone surgery or radiotherapy and the histopathological diagnosis included non-functioning pituitary adenoma [n=28 (16M/12F)], craniopharyngioma [n=4 (2M/2F)], meningioma (n=1F) and optic schwanomma (n=1F). Thirty subjects who demonstrated a maximal serum growth hormone (GH) concentration of 3ng/ml or less by an immunoradiometric assay (IRMA) after the insulin tolerance test (ITT) were diagnosed to have GH deficiency (GHD) [4] and were analyzed. They were grouped as Group 1 (15 Males) and Group 2 (15 females) and were analyzed separately. The female patients were subdivided in two groups as Group 2a: females with onset of GHD after 45years of age (n=8) and Group 2b: females with onset of GHD before 45 years of age (n=7). The age of onset of GHD was taken as age at which surgery for the central lesion was carried out. Thirty healthy controls, age, sex and body mass Index (BMI) matched with patients with no systemic disorders and on no medications were studied for similar parameters except for the ITT Test after their consent.

Laboratory analyses: Blood was collected after an overnight fast for biochemistry, serum lipid profile and hormonal evaluation; levels of serum insulin (RIA), serum insulin like growth factor-1 (IGF1) [IRMA-acid-alcohol extraction] and serum insulin like growth factor binding factor-3 (IGFBP3) [IRMA] were estimated by kit from DSL Inc, Webster, Tx. Insulin sensitivity was estimated, in the basal state, by use of the homeostasis model assessment (HOMA). The GH level was measured by IRMA kit -1900(DSL Inc, Webster, Tx) with standards calibrated to WHO first international standard (code 80/505:22k Da rhGH).

Body composition and bone mineral density: Dual energy X-ray absorptiometry (Hologic model QDR-4500) measurements included total hip, left femoral neck and lumbar spine. The short term in vivo precision (coefficients of variation %) in our unit was as follows: lumbar spine, 1.09%; femoral neck, 3.29%; and total hip, 1.26%.

Echocardiography: Cardiovascular function was assessed by two-dimensional, Mmode and Doppler echocardiography by a cardiologist blinded to study according to the standardization of the American Society of Echocardiography for left ventricular (LV) systolic and diastolic function and LV mass Index.

Carotid sonography: Intima-media thickness (IMT) was measured 1.5cm proximal to the carotid artery bifurcation, by high-resolution mode B ultrasound (mean of three measurements taken).

Quality of life (QoL) assessment: Adult growth hormone deficiency-specific quality of life (QoL-AGHDA): This questionnaire [5] consists of 25 questions with yes or no answers, relevant to the issues brought by GHD; lack of assertiveness, concentration, memory and energy; increased anxiety and depression; and difficulties in social interactions. A yes answer indicates that the patient perceives the problem. The sum of the number of yes answers is used as a measure of QoL, with a high score denoting an impaired QoL.

Statistics: Results are reported as the mean±SD. Comparisons were performed using two-tailed student's test (SPSS Software version 10.0) and P <0.05 was considered significant.


 :: Results Top


Baseline characteristics were similar between patients and controls except for increased waist-hip ratio (WHR) and lower IGF 1 and IGFBP3 in patients [Table - 1].

Body composition (DXA): In patients, Fat mass (FM) (%), truncal FM (%) was higher and lean body mass (LBM) (%), truncal LBM (%) was lower than controls [Table - 2].

Bone mineral density: The BMD was similar in Group 1 w.r.t controls. In female patients, BMD was significantly less than controls. Group 2a had BMD similar to controls, while Group 2b had significantly lower BMD [Table - 3].

Glucose homeostasis: There was no statistically significant difference between the mean sugars, insulin while HOMA IR [males 2.88±4.55 (patient) vs. 2.21±1.7(control), P value: 0.599(CI diff:−1.44 to3.1); females 3.63±4.2(patient) vs. 1.93±1.14(control), P value: 0.348(CI diff: −0.48 to 4.0)] tended to be higher in patients as compared to controls. The HOMA IR was 34% and 57% higher in male and female patients respectively than controls.

Lipid profile: Lipid parameters were similar in patients (MandF) and controls (data not shown). However, the lipid profile was abnormal {Triglycerides (TG)[mg/dl]:170.55±72.5(patient) vs. 101.24±31.0 (control); P -0.038 (CI diff: 1.76 to 86.51) and very low density lipoprotein cholesterol(VLDL)[mg/dl]: 33.54±14.9 (patient) vs. 20.25±6.18 (control); P- 0.05(CI diff: 1.86 to 21.7)}in Group 2b.

Echocardiography: Morphology, LV systolic and diastolic functions were similar in male patients and controls. In femalesthe Isovolumic relaxation time (IVRT) wassignificantly more than controls {108.7msec±20.1 (patient) vs. Controls 87.0msec±19.4 (controls); P = 0.006*(CI diff:10.4 to 36.9)}

Carotid IMT: The mean IMT in the right internal carotid {[male1.004±0.174: (patients) vs. 0.780±0.21 (control) P value:0. 04* (CI diff:0.13 to 0.42)]; [females: 0.946±0.154 (patient) vs. 0.662±0.206 (control) P value: 0.000*(95% CI of difference:0. 14-0.40)} and left internal carotid [male 1.008±0.243: (patients) vs. 0.791±0.23 (control) P value: 0.019* (CI diff:0.10 to 0.44)]; [females: 0.947±0.153 (patient) vs. 0.689±0.199 (control) P value: 0.000* (95% CI diff:0.12-0.38) }was significantly increased in comparison with the controls.

QoL: The AGHDA score {[male: 12.40±6.80 (patients) vs. 6.67±2.16 (control) P value: 0.004*(CI diff: 2.42 to 9.1)]; [females: 12.47±5.04 (patient) vs. 4.33±2.19 (control) P value: 0.000* (95% CI of difference: 4.65-6.4)} was significantly higher in male and female patients as compared to the controls.


 :: Discussion Top


To the best of our knowledge, this is the first study providing data about AOGHD patients in the Asian Indian population. Our patients with AOGHD showed altered BC with excess truncal fat mass similar to that reported in the literature. [6],[7],[8] Asian Indians have a unique body composition with greater waist circumference, excess truncal body fat and insulin resistance (IR) for a given BMI and thus have greater central obesity when compared with the Caucasians. [9],[10],[11] The IR denoted by HOMA IR tended to be high in our patient cohort, which is in agreement with the literature [12],[13],[14],[15] and could be accounted by the central obesity due to AOGHD.

In males and females (age >45 years) the lipid profile showed no difference. The lipid abnormalities (high TG, VLDL) were seen in only Group 2b (F <45 years) as reported earlier. [16],[17] Our findings of similar LDL [18],[19] and HDL levels are in keeping with the published literature. [19] Although abnormalities induced by inappropriate replacement of glucocorticoid and thyroxine (T4) [20] could contribute to dyslipidemia, patients in our study received replacement in the conventional manner and were proven to be euthyroid.

Earlier studies have shown evidence of cardiac dysfunction (diastolic and systolic) more convincingly with dynamic tests (stress echocardiography, radionuclide angiography, etc) especially with exercise [21],[22] though some studies have shown functional impairment at rest also. Cardiac parameters in our male patients were within the normal range which is in accordance with a previous study. [23] Interestingly, female patients had diastolic dysfunction at rest as in other studies. [21],[24]

The mean IMT in male and female patients of both carotids was significantly increased in comparison with the controls. Increased IMT, with more atheromatous plaques in the carotid and the femoral arteries, has been reported in GHD, compared with control subjects. [25],[26] These findings suggest increased cardiovascular risk in our cohort of AOGHD patients.

Various factors affect BMD in hypopituitary patients namely the age, severity, duration of GHD, inadequacy or overreplacement of the associated hormonal deficiencies and altered body composition. [10] In Group 1 and 2a there was no significant difference in BMD at various sites in comparison to the controls as shown in the literature. [27],[28],[29],[30] Our control population had osteopenia though they were healthy individuals and non-smokers. It is known that BMD at all sites in Indian population has been reported to be 5-15% lower than that in Caucasians, [31] which has been related to genetic reasons, smaller skeletal size of Indians and calcium and vitamin D malnutrition. Recent data indicates a high prevalence of vitamin D deficiency in urban Indians [32] though this is not assessed in the present study. In Group 2b BMD was significantly less in patients compared with controls. Due to very few patients below the age of 45 years we could not evaluate for similar changes in the male group. Our study highlights the age at onset of GHD as one of the important factors for the BMD changes though genetic and nutritional factors may also add to the derangement of metabolic health of our AOGHD patients.

Patients had significant impairment of QoL. Low QoL in hypopituitary adults at diagnosis [5] and its improvement after GH therapy have been demonstrated in earlier studies. [33] The individuals with the lowest QoL had the most improvement after GH treatment.

There are certain limitations to the study, namely cross-sectional design and lower number of patients in each subgroup. Ideally, AOGHD patients should have been compared with patients with hypothalamopituitary disease having normal GH level, which would have unequivocally proven the results to be due to GHD. It would be interesting to start GH therapy in all the patients and quantify the response in all the various parameters according to the age of onset of GHD.

To summarize, male patients and females more than 45years with AOGHD syndrome have central obesity, increased cardiovascular risk (increased IMT) and poor quality of life while BMD was not affected. Younger AOGHD female patients less than 45 years of age have most of the features of classical AOGHD syndrome and would be the group to benefit maximally with rhGH treatment which is important in a resource constraint situation.


 :: Acknowledgment Top


We would like to acknowledge help of Scientific Officers Mrs. Anjana Karvat and Mr. Harshavardhan Powar.

 
 :: References Top

1.S φnksen PH. Replacement therapy in hypothalamo-pituitary insufficiency after childhood: Management in the adult. Horm Res 1990;33:45-51.  Back to cited text no. 1    
2.Jψrgensen JO, Pedersen SA, Thuesen L, Jψrgensen J, Ingemann-Hansen T, Skakkebaek NE. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1989;1:1221-5.  Back to cited text no. 2    
3.Gibney J, Wallace JD, Spinks T, Schnorr L, Ranicar A, Cuneo RC, etal. The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Metab 1999;84:2596-602.  Back to cited text no. 3    
4.Corneli G, Gasco V, Prodam F, Grottoli S, Aimaretti G, Ghigo E. Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood. Pituitary 2007;10:141-9.  Back to cited text no. 4    
5.McKenna SP, Doward LC, Alonso J, Kohlmann T, Niero M, Prieto L, et al. The QoL-AGHDA: An instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res 1999;8:373-83.  Back to cited text no. 5    
6.Hoffman AR, Kuntze JE, Baptista J, Baum HB, Baumann GP, BillerBM, et al. Growth Hormone (GH) replacement therapy in adult-onset GH deficiency: Effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004;89:2048-56.  Back to cited text no. 6    
7.Murray RD, Adams JE, Shalet SM. Adults with partial growth hormone deficiency have an adverse body composition. J Clin Endocrinol Metab 2004; 89:1586-91.  Back to cited text no. 7    
8.Koranyi J, Bosaeus I, Alpsten M, Bengtsson BA, Johannsson G. Body composition during GH replacement in adults-methodological variations with respect to gender. Eur J Endocrinol 2006;154:545-53.  Back to cited text no. 8    
9.Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007;125:217-30.  Back to cited text no. 9    
10.Raji A, Seely EW, Arky RA, Simonson DC. Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 2001;86:5366-71.  Back to cited text no. 10    
11.Misra A, Misra R, Wijesuriya M, Banerjee D. The metabolic syndrome in South Asians: Continuing escalation and possible solutions. Indian J Med Res 2007;125:345-54.  Back to cited text no. 11    
12.Salomon F, Cureo RC, Umpleby AM, Sonksen PH. Glucose and fat metabolism in adults with growth hormone deficiency. Clin Endocrinol 1994;41:315-22.  Back to cited text no. 12    
13.Hew FL, Koschmann M, Christopher M, et al. Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity. J Clin Endocrinol Metab 1996;81:555-64.  Back to cited text no. 13    
14.Svensson J, Fowelin J, Landin K, Bengtsson BA, Johansson JO. Effects of seven years of GH-replacement therapy on insulin sensitivity in GH-deficient adults. J Clin Endocrinol Metab 2002;87:2121-7.  Back to cited text no. 14    
15.Johansson JO, Fowelin J, Landin K, Lager I, Bengtsson BA. Growth hormone-deficient adults are insulin resistant. Metab Clin Exp 1995;44:1126-9.  Back to cited text no. 15    
16.Al-Shoumer KA, Cox KH, Hughes CL, Richmond W, Johnston DG. Fasting and post prandial lipid abnormalities in hypopituitary women receiving conventional replacement therapy. J Clin Endocrinol Metab 1997;82:2653-9.  Back to cited text no. 16    
17.Packard CJ, Shepherd J. Lipoprotein heterogeneity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol 1997;17:3542-56.  Back to cited text no. 17    
18.Christ ER, Cummings MH, Stolinski M, Jackson N, Lumb PJ, Wierzbicki AS, et al. Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: A stable isotope study. Eur J Endocrinol 2006;154:459-66.  Back to cited text no. 18    
19.Twickler TB, Wilmink HW, Schreuder PC, Cabezas MC, van Dam PS, Koppeschaar HP, et al. Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency. J Clin Endocrinol Metab 2000;85:4683-9.  Back to cited text no. 19    
20.Al-Shoumer, AliAnyaoka, Nithyanathan R. Overnight metabolic fuel deficiency in patients treated conventionally for hypopituitarism. Clin Endocrinol 1996;45:171-8.  Back to cited text no. 20    
21.Colao A, Cuocolo A, Di Somma C, Cerbone G, Della Morte AM, NicolaiE, et al. Impaired cardiac performance in elderly patients with growth hormone deficiency. J Clin Endocrinol Metab 1999;84:3950-5.  Back to cited text no. 21    
22.Cuneo RC. GH and cardiac failure. J Clin Endocrinol Metab 2001;86:4635-7.  Back to cited text no. 22    
23.Shahi M, Beshyah SA, Hackett D, Sharp PS, Johnston DG, FoaleRA. Myocardial dysfunction in treated adult hypopituitarism: A possible explanation for increased cardiovascular mortality. Br Heart J 1992;67:92-6.  Back to cited text no. 23    
24.Dougherty AH, Naccerelli GV, Grey EL, Hicks CH, Golstein RA. Congestive heart failure with normal systolic function. Am J Cardiol 1987; 54:778-82.  Back to cited text no. 24    
25.Furberg CD, Adams HP Jr, Applegate WB, Byington RP, Espeland MA, Hartwell T, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation 1994;90:1679-87.  Back to cited text no. 25    
26.Gola M, Bonadonna S, Doga M, Giustina A. Clinical review: Growth hormone and cardiovascular risk factors. J Clin Endocrinol Metab 2005;90:1864-70.  Back to cited text no. 26    
27.Janssen YJ, Hamdy NA, Fr φlich M, Roelfsema F. Skeletal effects of two years of treatment with low physiological doses of recombinant human growth hormone (GH) in patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1998;83:2143-8.  Back to cited text no. 27    
28.Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML, et al. Evaluation and treatment of adult growth hormone deficiency: A endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1621-34.  Back to cited text no. 28    
29.Toogood AA, Adams JE, O'Neill PA, Shalet SM. Elderly patients with adult-onset growth hormone deficiency are not osteopenic. J Clin Endocrinol Metab 1997;82:1462-6.  Back to cited text no. 29    
30.Murray RD, Columb B, Adams JE, Shalet SM. Low bone mass is an infrequent feature of the adult growth hormone deficiency syndrome in middle-age adults and the elderly. J Clin Endocrinol Metab 2004;89:1124-30.  Back to cited text no. 30    
31.Tandon N, Marwaha RK, Kalra S, Gupta N, Dudha A, Kochupillai N. Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability. Natl Med J India 2003;16:298-302.  Back to cited text no. 31    
32.Mithal A. Bone mineral health of Indians. Natl Med J India 2003;16:294-7.  Back to cited text no. 32    
33.Woodhouse LJ, Mukherjee A, Shalet SM, Ezzat S. The influence of growth hormone status on physical impairments, functional limitations and health-related quality of life in adults. Endocr Rev 2006;27:287-317.  Back to cited text no. 33    



 
 
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  [Table - 1], [Table - 2], [Table - 3]

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