Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Heredity and Symptoms in Acromegaly J. E. G. Kinnman To cite this article: J. E. G. Kinnman (1976) Heredity and Symptoms in Acromegaly, Acta OtoLaryngologica, 82:1-6, 230-233, DOI: 10.3109/00016487609120891 To link to this article: http://dx.doi.org/10.3109/00016487609120891
Published online: 08 Jul 2009.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [University of California, San Diego]
Date: 25 March 2016, At: 16:12
Acta Otolaryngol82: 230-233, 1976
HEREDITY AND SYMPTOMS IN ACROMEGALY
J. E. G. Kinnman
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
From the Department of Otolaryngology, Karolinska sjukhuset, and King Gustaf V Research Institute, Stockholm, Sweden
Abstract. The author has performed clinical and followup studies of 80 acromegalic patients treated by transanthro-sphenoidal removal of the pituitary adenoma. Heredity for acromegaly or gigantism was recorded in 3.8% of the patients and other hereditary factors in 13.8%. Head trauma, meningitis or encephalitis was recorded in the case histories in 18.8%. The predominant symptoms were sweating, paraesthesiae, headache and joint pain. Acromegaly was in 37.6% associated with goitre, parathyroid adenoma, gastric or duodenal ulcer, parotid tumours or submandibular swelling. The fecundity among the married patients was good, 34.4% having three or more children. Successful pregnancies occurred after the transanthro-sphenoidal removal of the adenoma.
Acromegaly is a disease which, untreated, leads to significant disability and shortening of life expectancy through intracranial extension of the tumour, diabetes mellitus, hypermetabolism, splanchnomegaly and, ultimately heart failure. The life expectancy of acromegalic patients is shorter than that of patients suffering from non-functioning “chromophobic” adenoma (Bakay, 1950). Deaths in acromegalic patients is more often due to secondary effects of STH (somatotropic hormone) overproduction than to local effects of the tumour (Henderson, 1938). Davidoff (1926) stated that hereditary influences on the disease exist although only 4 of the 100 patients in his series had a definite family history of acromegaly. A frequent early symptom of acromegaly is amenorrhoea in women and impotence and/ or decreased libido in men (Marie, 1886, 1890; Cushing, 1909). Davidoff (1926), in his Actu Otoluryngol82
series of 100 patients with acromegaly, observed that the fecundity was below the usual average, and the number of children born to those who married after the onset of the disease was small.
CASE MATERIAL During the period 1961-1972, 47 male and 33 female patients with acromegaly were treated with transanthro-sphenoidal surgery for removal of the pituitary adenoma. At operation the majority of patients (approx. 62 %) were in the age group from 41 to 60 years. The average age at onset of the disease was estimated to be 34.8 years. Only in three (male) patients did the family history reveal that several members were of high stature. Diabetes mellitus occurred among relatives in five patients, goitre in three, gastric ulcer in one, epilepsy in one and osteogenesis imperfecta with otosclerosis in one (Table I). In four male patients, primary hyperparathyroidism had been established-goitre had been diagnosed in two of these patients, and one of them also suffered from duodenal ulcer and otosclerosis. One of the patients in this group had a pronounced submandibular gland swelling and marked dryness of the mouth. One patient had been operated on for a carpal tunnel syndrome 5 years prior to the
Heredity and symptoms in acromegaly Table I. Hereditary factors, previous diseases and fecundity in 80 acromegalic patients Values within parentheses are percentages
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
Males Hered. for acromeg. or gigantism Other hered. factors Head trauma Meningitis Encephalitis Goitre Parathyr, adenoma Gastric or duodenal ulcer Varicose veins Haemorrhoids Parotid tumour Swelling of submandibular gland Hearing dist. Hernia Arnold-Chiari anomaly Epilepsy
Females
Total
3 (6.4) 7 (14.9) 7 (14.9) 0 1 4 (8.5) 4 (8.5)
0 4 (12.1) 3 (9.1) 2 (6.1) 2 (6.1) 9(27.3) 0
3 (3.8) 11 (13.8) 10 (12.5) 2 (2.5) 3 (3.8) 13 (16.3) 4 (5)
6 (12.8)
2 (6.1) 3 (9.1) 1 1
8 (10) 4 (5) 7 (8.8) 2 (2.5)
2 (4.3) 3 (6.4) 9 (19.1)
1 0
3 (3.8) 3 (3.8) 10 (12.5)
0 0
2 (6.1) 2 (6.1)
1
6(12.8) 1
1
Fecundity among married patients (n=61) No children 4 (11.1) 6 (24.0) One 11 (30.5) 6 (24.0) Two 10 (27.8) 3 (12.0) Three 5 (13.9) 5 (20.0) More than three 6 (16.7) 5 (20.0)
23 1
struation occurred in 78.7% of the women. At the time of operation impotence and/or decreased sexual libido were seen in 53.2% of the male patients. Psychic disturbances, mainly in the form of moderate depression, occurred in 36.2% among the male patients and in 30.3 % among the females. At the time of operation signs of ACTH insufficiency occurred in 18.8 % of the patients, TSH in 13.8% and ADH (antidiuretic hormone) in 7.5 %. Pathological intravenous glucose tolerance test was seen in 59.5% of the patients preoperatively-the postoperative regression rate of acromegalic activity seemed to be best correlated to a restitution of normal glucose tolerance.
2 (2.5) 2 (2.5)
DISCUSSION 10 (16.4) 17 (27.9) 13 (21.3) 10 (16.4) 11 (18.0)
transanthro-sphenoidal surgery. In another patient, a small mammary carcinoma was detected at the time when she was admitted for pituitary surgery. Ten of the married patients were childless, but 34 % had from 3 to 9 children. The weight, height, blood pressure and heart volumes are listed in Table 11. Increased pigmentation was seen in 14.9% of the males and in 12.1% of the females. Hypertrichosis was seen in 36.2 % and in 39.4 %, respectively. Increased perspiration was the most common symptom followed by paraesthesiae, headache and joint pain. At the last follow-up, total regression of the main symptoms was noted in somewhat 70 % of the patients (Table 111). Total regression or improvement of the clinical signs and symptoms of acromegalic activity was seen in 93.8% of the patients. Secondary amenorrhoea or irregular men-
The most commonly postulated theory of tumour genesis in the pituitary gland is that of increased hypophysiotropic stimulation from the hypothalamus-in some cases possibly induced by a primary end organ deficiency (Russfield, 1968; Pelletier, 1971; Doniach, 1972). STH uniquiely can stimulate both normal and supranormal growth. Many factors are known to stimulate the STH releaseamong these are hypoglycaemia, prolonged fasting, exercise, anaesthesia, surgery and trauma (Glick et al., 1965; Trenkle, 1970; Carey et al., 1971; Buckler, 1972). Theoretically, head trauma may disturb the hypothalamic centre for the control of STH secretion. Encephalitis and meningitis may act in the same way. In acromegaly, the frequent co-existence of goitre, the frequent occurrence of latent or manifest diabetes mellitus, amenorrhoea, hyperpigmentation and asthenia suggest a participation of the thyroid, pancreatic islets, ovary and adrenal glands. These symptoms have been grouped together under the heading of polyglandular syndrome (Cushing, 1912). It has been suggested that STH may produce tumours in a number of organ sysActn Otolnryngol82
232
J . E. G. Kinnman
Table 11. Height, weight, STH, blood pressure and relative heart volume in 80 acromegalic patients At operation
Males Height, cm
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
Weight
STH, ng/ml
n =47 mean: 179.5 range: 166-207 n =47 mean: 92.2 range: 66-127
n =45
n =38
n =46 mean: 9.7 range: 1.3-50.0
mean: 55.0 range: 6-283 Blood press., mmHg systolic
diastolic
Heart vol.
Females Height, cm
Weight, kg
STH, ng/ml
Blood press., mmHg systolic
diastolic
Heart vol., ml/m2
At last follow-up
mean: 92.8 range: 66-137
n =47 mean: 155 range: 110-210
n =45
n =47 mean: 95 range: 60-160
n =45
n=32 mean: 488 range: 350-720
n=18 mean: 490 range: 2 W O O
mean: 149 range: 110-200 mean: 92 range: 60-130
n=33 mean: 165.4 range: 152-174 n =33 mean: 67.7 range: 54-78 n=27 mean: 64.3 range: 6-520
n=33 mean: 70.3 range: 54-81 n =32 mean: 50.2 range: 1.6-1.OOO
n=33 mean: 152 range: 100-220
n=33 mean: 150 range: 11C~200
n =33 mean: 95 range: 60-125 n=21 mean: 432 range: 300420
n=33 mean: 92 range: 70-120 n =8 mean: 443 range: 370-530
tems, and acromegaly may be associated with pheochromocytoma, goitre, diabetes mellitus and endometriosis (Miller & Wynn, 1971). Peptic ulcers antedate the pituitary symptoms by 5 to 10 years and is often fulminating and intractable (Roth & Vilardell, 1960). Acta Otolaryngol82
Hyperplasia of the submandibular glands in acromegalic patients has been observed occasionally (Benda, 1901; Ardran & Kemp, 1972) -the combination of pleomorphic adenoma of the parotid gland with acromegaly has been reported by Gadrat et al., 1970. In a polysymptomatic disease as acromegaly the question must, however, always be put whether one or several of the symptoms and signs may be caused by a co-existent pathological condition. From the present relatively large series no definite conclusions can be drawn as regards the influence of genetic factors in acromegaly. Such factors may, however, come to play a greater role in the future since the fecundity among the patients seems to be good, and successful pregnancies without re-activation of the disease have been observed after the transanthro-sphenoidal operation of the pituitary adenoma. In this series the operation resulted in a high rate of regression of the acromegalic symptoms and at the same time normal anterior pituitary function was often restored.
ZUSAMMENFASSUNG Der Verfasser hat eine klinische und Nachuntersuchung an 80 Akromegalien unternommen, die mit der transantro-sphenoidalen Operation des Hypophysentumors behandelt waren. Hereditat fur Akromegalie oder Gigantismus wurde in 3,8% der Patienten gefunden und an-
Table 111. Symptoms and signs in 80 acromegalic patients RegresAt At last sion operation follow-up (%) Sweating Paraesthesia Headache Joint pain Soft-tissue swelling Face Hands and feet Skeletal changes Head and face Hands and feet
72 (90.0) 54 (67.5) 48 (60.0) 37 (46.3)
19 (23.8) 14 (17.5) 11 (13.8) 10 (12.5)
73.6 74.1 77.1 72.9
79 (98.8) 79 (98.8)
48 (60.0) 55 (68.7)
39.3 30.4
76 (95.0) 71 (88.8)
76 (95.0) 71 (88.8)
0 0
Heredity and symptoms in acromegaly
mandibularis begleitet. Ungefahr 34% der verheirateten Patienten hatten drei oder mehr Kinder. Einige Patienten hatten nach der Hypophysenoperation eine normale Schwangerschaft. Reference list can be required f r o m the author.
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
dere hereditare Faktoren in 13,8%, Schadeltrauma, Meningitis oder Encephalitis in 18,8%. Die dominierenden Syrnptome waren Schwitzen, Parasthesien, Kopf- und Gelenkschmerzen. Die Akromegalie war in 37,6% von Kropf. Parathyreoideadenome, Ulcus ventriculi oder duodeni, Parotistumor oder Schwellung der Glandula sub-
233
Acta Otolaryngol82
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Heredity and Symptoms in Acromegaly J. E. G. Kinnman To cite this article: J. E. G. Kinnman (1976) Heredity and Symptoms in Acromegaly, Acta OtoLaryngologica, 82:1-6, 230-233, DOI: 10.3109/00016487609120891 To link to this article: http://dx.doi.org/10.3109/00016487609120891
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 1
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [University of California, San Diego]
Date: 25 March 2016, At: 16:12
Acta Otolaryngol82: 230-233, 1976
HEREDITY AND SYMPTOMS IN ACROMEGALY
J. E. G. Kinnman
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
From the Department of Otolaryngology, Karolinska sjukhuset, and King Gustaf V Research Institute, Stockholm, Sweden
Abstract. The author has performed clinical and followup studies of 80 acromegalic patients treated by transanthro-sphenoidal removal of the pituitary adenoma. Heredity for acromegaly or gigantism was recorded in 3.8% of the patients and other hereditary factors in 13.8%. Head trauma, meningitis or encephalitis was recorded in the case histories in 18.8%. The predominant symptoms were sweating, paraesthesiae, headache and joint pain. Acromegaly was in 37.6% associated with goitre, parathyroid adenoma, gastric or duodenal ulcer, parotid tumours or submandibular swelling. The fecundity among the married patients was good, 34.4% having three or more children. Successful pregnancies occurred after the transanthro-sphenoidal removal of the adenoma.
Acromegaly is a disease which, untreated, leads to significant disability and shortening of life expectancy through intracranial extension of the tumour, diabetes mellitus, hypermetabolism, splanchnomegaly and, ultimately heart failure. The life expectancy of acromegalic patients is shorter than that of patients suffering from non-functioning “chromophobic” adenoma (Bakay, 1950). Deaths in acromegalic patients is more often due to secondary effects of STH (somatotropic hormone) overproduction than to local effects of the tumour (Henderson, 1938). Davidoff (1926) stated that hereditary influences on the disease exist although only 4 of the 100 patients in his series had a definite family history of acromegaly. A frequent early symptom of acromegaly is amenorrhoea in women and impotence and/ or decreased libido in men (Marie, 1886, 1890; Cushing, 1909). Davidoff (1926), in his Actu Otoluryngol82
series of 100 patients with acromegaly, observed that the fecundity was below the usual average, and the number of children born to those who married after the onset of the disease was small.
CASE MATERIAL During the period 1961-1972, 47 male and 33 female patients with acromegaly were treated with transanthro-sphenoidal surgery for removal of the pituitary adenoma. At operation the majority of patients (approx. 62 %) were in the age group from 41 to 60 years. The average age at onset of the disease was estimated to be 34.8 years. Only in three (male) patients did the family history reveal that several members were of high stature. Diabetes mellitus occurred among relatives in five patients, goitre in three, gastric ulcer in one, epilepsy in one and osteogenesis imperfecta with otosclerosis in one (Table I). In four male patients, primary hyperparathyroidism had been established-goitre had been diagnosed in two of these patients, and one of them also suffered from duodenal ulcer and otosclerosis. One of the patients in this group had a pronounced submandibular gland swelling and marked dryness of the mouth. One patient had been operated on for a carpal tunnel syndrome 5 years prior to the
Heredity and symptoms in acromegaly Table I. Hereditary factors, previous diseases and fecundity in 80 acromegalic patients Values within parentheses are percentages
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
Males Hered. for acromeg. or gigantism Other hered. factors Head trauma Meningitis Encephalitis Goitre Parathyr, adenoma Gastric or duodenal ulcer Varicose veins Haemorrhoids Parotid tumour Swelling of submandibular gland Hearing dist. Hernia Arnold-Chiari anomaly Epilepsy
Females
Total
3 (6.4) 7 (14.9) 7 (14.9) 0 1 4 (8.5) 4 (8.5)
0 4 (12.1) 3 (9.1) 2 (6.1) 2 (6.1) 9(27.3) 0
3 (3.8) 11 (13.8) 10 (12.5) 2 (2.5) 3 (3.8) 13 (16.3) 4 (5)
6 (12.8)
2 (6.1) 3 (9.1) 1 1
8 (10) 4 (5) 7 (8.8) 2 (2.5)
2 (4.3) 3 (6.4) 9 (19.1)
1 0
3 (3.8) 3 (3.8) 10 (12.5)
0 0
2 (6.1) 2 (6.1)
1
6(12.8) 1
1
Fecundity among married patients (n=61) No children 4 (11.1) 6 (24.0) One 11 (30.5) 6 (24.0) Two 10 (27.8) 3 (12.0) Three 5 (13.9) 5 (20.0) More than three 6 (16.7) 5 (20.0)
23 1
struation occurred in 78.7% of the women. At the time of operation impotence and/or decreased sexual libido were seen in 53.2% of the male patients. Psychic disturbances, mainly in the form of moderate depression, occurred in 36.2% among the male patients and in 30.3 % among the females. At the time of operation signs of ACTH insufficiency occurred in 18.8 % of the patients, TSH in 13.8% and ADH (antidiuretic hormone) in 7.5 %. Pathological intravenous glucose tolerance test was seen in 59.5% of the patients preoperatively-the postoperative regression rate of acromegalic activity seemed to be best correlated to a restitution of normal glucose tolerance.
2 (2.5) 2 (2.5)
DISCUSSION 10 (16.4) 17 (27.9) 13 (21.3) 10 (16.4) 11 (18.0)
transanthro-sphenoidal surgery. In another patient, a small mammary carcinoma was detected at the time when she was admitted for pituitary surgery. Ten of the married patients were childless, but 34 % had from 3 to 9 children. The weight, height, blood pressure and heart volumes are listed in Table 11. Increased pigmentation was seen in 14.9% of the males and in 12.1% of the females. Hypertrichosis was seen in 36.2 % and in 39.4 %, respectively. Increased perspiration was the most common symptom followed by paraesthesiae, headache and joint pain. At the last follow-up, total regression of the main symptoms was noted in somewhat 70 % of the patients (Table 111). Total regression or improvement of the clinical signs and symptoms of acromegalic activity was seen in 93.8% of the patients. Secondary amenorrhoea or irregular men-
The most commonly postulated theory of tumour genesis in the pituitary gland is that of increased hypophysiotropic stimulation from the hypothalamus-in some cases possibly induced by a primary end organ deficiency (Russfield, 1968; Pelletier, 1971; Doniach, 1972). STH uniquiely can stimulate both normal and supranormal growth. Many factors are known to stimulate the STH releaseamong these are hypoglycaemia, prolonged fasting, exercise, anaesthesia, surgery and trauma (Glick et al., 1965; Trenkle, 1970; Carey et al., 1971; Buckler, 1972). Theoretically, head trauma may disturb the hypothalamic centre for the control of STH secretion. Encephalitis and meningitis may act in the same way. In acromegaly, the frequent co-existence of goitre, the frequent occurrence of latent or manifest diabetes mellitus, amenorrhoea, hyperpigmentation and asthenia suggest a participation of the thyroid, pancreatic islets, ovary and adrenal glands. These symptoms have been grouped together under the heading of polyglandular syndrome (Cushing, 1912). It has been suggested that STH may produce tumours in a number of organ sysActn Otolnryngol82
232
J . E. G. Kinnman
Table 11. Height, weight, STH, blood pressure and relative heart volume in 80 acromegalic patients At operation
Males Height, cm
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
Weight
STH, ng/ml
n =47 mean: 179.5 range: 166-207 n =47 mean: 92.2 range: 66-127
n =45
n =38
n =46 mean: 9.7 range: 1.3-50.0
mean: 55.0 range: 6-283 Blood press., mmHg systolic
diastolic
Heart vol.
Females Height, cm
Weight, kg
STH, ng/ml
Blood press., mmHg systolic
diastolic
Heart vol., ml/m2
At last follow-up
mean: 92.8 range: 66-137
n =47 mean: 155 range: 110-210
n =45
n =47 mean: 95 range: 60-160
n =45
n=32 mean: 488 range: 350-720
n=18 mean: 490 range: 2 W O O
mean: 149 range: 110-200 mean: 92 range: 60-130
n=33 mean: 165.4 range: 152-174 n =33 mean: 67.7 range: 54-78 n=27 mean: 64.3 range: 6-520
n=33 mean: 70.3 range: 54-81 n =32 mean: 50.2 range: 1.6-1.OOO
n=33 mean: 152 range: 100-220
n=33 mean: 150 range: 11C~200
n =33 mean: 95 range: 60-125 n=21 mean: 432 range: 300420
n=33 mean: 92 range: 70-120 n =8 mean: 443 range: 370-530
tems, and acromegaly may be associated with pheochromocytoma, goitre, diabetes mellitus and endometriosis (Miller & Wynn, 1971). Peptic ulcers antedate the pituitary symptoms by 5 to 10 years and is often fulminating and intractable (Roth & Vilardell, 1960). Acta Otolaryngol82
Hyperplasia of the submandibular glands in acromegalic patients has been observed occasionally (Benda, 1901; Ardran & Kemp, 1972) -the combination of pleomorphic adenoma of the parotid gland with acromegaly has been reported by Gadrat et al., 1970. In a polysymptomatic disease as acromegaly the question must, however, always be put whether one or several of the symptoms and signs may be caused by a co-existent pathological condition. From the present relatively large series no definite conclusions can be drawn as regards the influence of genetic factors in acromegaly. Such factors may, however, come to play a greater role in the future since the fecundity among the patients seems to be good, and successful pregnancies without re-activation of the disease have been observed after the transanthro-sphenoidal operation of the pituitary adenoma. In this series the operation resulted in a high rate of regression of the acromegalic symptoms and at the same time normal anterior pituitary function was often restored.
ZUSAMMENFASSUNG Der Verfasser hat eine klinische und Nachuntersuchung an 80 Akromegalien unternommen, die mit der transantro-sphenoidalen Operation des Hypophysentumors behandelt waren. Hereditat fur Akromegalie oder Gigantismus wurde in 3,8% der Patienten gefunden und an-
Table 111. Symptoms and signs in 80 acromegalic patients RegresAt At last sion operation follow-up (%) Sweating Paraesthesia Headache Joint pain Soft-tissue swelling Face Hands and feet Skeletal changes Head and face Hands and feet
72 (90.0) 54 (67.5) 48 (60.0) 37 (46.3)
19 (23.8) 14 (17.5) 11 (13.8) 10 (12.5)
73.6 74.1 77.1 72.9
79 (98.8) 79 (98.8)
48 (60.0) 55 (68.7)
39.3 30.4
76 (95.0) 71 (88.8)
76 (95.0) 71 (88.8)
0 0
Heredity and symptoms in acromegaly
mandibularis begleitet. Ungefahr 34% der verheirateten Patienten hatten drei oder mehr Kinder. Einige Patienten hatten nach der Hypophysenoperation eine normale Schwangerschaft. Reference list can be required f r o m the author.
Downloaded by [University of California, San Diego] at 16:12 25 March 2016
dere hereditare Faktoren in 13,8%, Schadeltrauma, Meningitis oder Encephalitis in 18,8%. Die dominierenden Syrnptome waren Schwitzen, Parasthesien, Kopf- und Gelenkschmerzen. Die Akromegalie war in 37,6% von Kropf. Parathyreoideadenome, Ulcus ventriculi oder duodeni, Parotistumor oder Schwellung der Glandula sub-
233
Acta Otolaryngol82
