Guide to the physical features of acromegaly and gigantism 

"L'acromegalie est la gigantisme de l'adulte, le gigantisme est l'acromegalie de l'adolescent." Pierre Marie 1886

This chapter is designed as a guide to the physical features seen in 'historical' acromegaly so should not in any way be viewed as the current state of treatment. Many of the characteristics portrayed are the consequences of untreated acromegaly. Some characteristics develop in all acromegalics especially soft tissue changes but these usually decrease in severity with treatment. For the current state of treatment and support please follow the link through to the Pituitary Foundation website.

Aetiology and biochemistry

Tumour type: Basophilic adenoma

Biochemical effects: Increased secretion of growth hormone

Effects on tissue biochemistry

Other hormones

Raised BMR

Non-effect on age changes, puberty and ageing still occur to the standard pattern. Pattern of hormone changes.

Hypertrophy of the sweat glands - attacks of sweating. Paraesthesia of the fingers (Normal serum calcitonin) in an early active disease involving all fingers.

Biochemical changes

Polydipsia/ Diabetes Mellitus

Raise BMR other parameters of thyroid are usually normal (rarely thyrotoxicosis may co-exist 1.11)

Effect on other glands e.g. Adrenal

Decreased pigmentation (Science J colour) due to a lack of in hands.

More than acromegaly

Relationship between gigantism, acromegaly and acromegalic gigantism

At first each of these were regarded as separate conditions and acromegalic-gigantism was regarded as a confusion or only recognised as gigantism or acromegaly. The position was clearer by the 1900's as the root cause of the disease, the pituitary adenoma, was found in gigantism and acromegaly alike.

The normal sequence of changes from child via puberty to adulthood occur regardless of the tumour and its oversecretion of growth hormone, so what form the conditions takes depends purely on its time of onset. An early onset leads to gigantism with excessive growth of the epiphyses leading to increased height but proportions are kept the same, then as puberty occurs it is followed by progressive acromegalic changes leading to a picture of a giant with acromegalic features - acromegalic gigantism. When onset is later, after epiphyseal closure, only acromegaly results.

Diagram to show change with age due to oversecretion of growth hormone.

Major symptoms in the stages of acromegalic deformity

1. Without deformity:
   • Hypertrophy of sebaceous glands, excessive sweating
   • Paraesthesia, general in all fingers usually the earliest neurological symptom
   • Sella turcica may be entirely normal or Occasionally, headaches, gynaecomastia and galactorrhea.
2. Progressive deformity:
   • Radiologic changes, e.g. tufting distal phalanges
   • Increased skin thickness, e.g. heel pad
3. Advanced deformity:
   • Cardiovascular and neuroarticular disease
   • Diabetes mellitus and ultimately hypopituitarism
   • Initial effect 1°, 2, 3 effects of hormonal changes.
   • Dysfunction Centres affected by growth hormone direct and indirect.

Soft tissues

Changes in the soft tissues are one of the most characteristic of acromegalic features, the ‘acro’ extremities bearing the brunt of these changes, but other areas of the body can be and often are just as affected with severe consequences.

Hands and feet

Joint changes

Carpal tunnel syndrome and amyotrophy

Skin and adnexae

Nasal and oropharyngeal changes

1.3.1 Hands and feet

These ‘extremities’ were the main features that led to the differential diagnosis of acromegaly, whatever else occurred the hands and feet were always enlarged. The hands have been variously described as battledore (racquet, bat or paddle shaped), ‘main capitonées’ (Péchadre), spade-like, sausage-like fingers (Marie). The enlargement of the hands begins from the wrists, which are slightly affected, the forearms are unaffected or may be thinner due to amyotrophy. The characteristic appearance is in the contrast between the large hands and disproportionately slender arm.

Than hands are very large and broad, but not deformed, the furrows of the skin are deep, the folds puffy, the interphalangeal folds of the knuckles being especially distinct. Radiographs show the metacarpals pressed away from each other and the ends of the bones widely separated due to this tissue overgrowth.

The fingers as a whole are cylindrical and flattened from the dorsum to the palm since their circumference at the base end is proportionately increased so the comparison to little sausages, with drumstick-like pads at the tips. The nails are unaffected contrasting with the enlarged fingers.

Two types of hands were described by Marie “type en long” and type en large” or “type massif”, the latter being more usual; a broad massive spade-like hand, where the bones are thickened and end with osteophytes common.

Enlargement in the hands in the later stages is due to bony growth, thickening of the diaphysis and at the tips of the fingers tufting.

In gigantism the hands and tissues enlarge proportionately with the rest of the body and bones, but though the growth is abnormal the proportions are not.

“ The size of her gloves increased steadily from No 6 1/2 to 8 and her shoemaker was troubled with the difficulty of procuring ‘tops’ remarking with somewhat ungallant candour that he had never known a woman to have so large a foot.” Whyte Mackie, J 1893

In the same way as the hands, the feet are enormously bulky and flat, the toes thick and coarse, with the increased heel pad thickness (Kho et al 1970). The enlargement doesn't extend above the ankles and the leg muscles are often decreased in size.

The increase in size of the hands and feet due to the soft tissue isn’t continuous, may become stationary or decrease depending on the disease condition or following treatment.

The practical problems resulting from enlargement of the hands and feet were often the signs first recognised by the sufferer and the medical profession. Growth is often so rapid that new gloves and boots were constantly required (Whyte Mackie J 1893) also rings and thimbles. Fingers getting caught in the keys whilst playing the organ Appleyard 1892.

The contours of the acromegalic depends essentially on the changes in the osseous system overlaid by the changes in the skin and adjacent soft tissues.

" The next case is that of a giantess from Missouri, named Ella Ewing, whom I discovered on exhibition at a Western State Fair. I regret extremely my inability to give accurate measurements in this case, which proved impossible, partly from the natural modesty of the young lady in question, and partly from the well-known reluctance of exhibits of this description to submit to accurate measurements. Her height was given at 8' 2", her age 23, and her weight 256 Ibs, but my own estimate of her height compared with normal persons of known height would be 7' 6". Hutchinson 1898

In fact, so apparent was the tremendous elongation of her lower limbs that I was inclined to suspect that her height had been added to by means of some form of stilt. Direct investigations on this suspicion was, of course, out of the question, in view of her sex; but after careful watching I succeeded in getting a good view of her feet, which at once dispelled any suspicions. They were of such enormous size and clumsy shape that no woman of any age, giantess or otherwise would have dreamed of counterfeiting them.

". . . While it would be impossible to make any definite statement, the impression made by the appearance of the girl, of the excessive development of both upper and lower extremities, the shape of her hands, the disproportionate size of both jaws, as also of the nose and the lisping speech, I should be inclined to regard the case as an early stage of acromegaly contiguous with the gigantism which started, by her account, at the age of nine......" Hutchinson 1898

Woods Hutchinson, Professor of Comparative Pathology, Univ. of Buffalo, New York Medical Journal, Vol. 72 Pages 93/4

Effect on hands and feet

• Flemming P 1890
• Barclay C 892
• Bab H 913
• Williamson CS 1915-16
• Walton AJ 1921
• London DR 1976
• Schereschewsky 1926 Gig changes
• Renader A 1937
• Sanders MD 1966
• Sternberg M 1899 Casts of hands two different types.

1.3.2 Joint changes

Initial changes occur before the stage of deformity is reached; soft tissue enlargement leads to excessive and abnormal joint mobility, with recurrent effusions which may be large further stretching capsules and ligaments, and thickening of bursae.

Radiologically joint spaces are increased. Straight leg raising is increased to a mean of 130° an unusual finding in anyone over 30.

As a secondary process and less commonly massive bony outgrowths, exostoses, produce sever limitation of movement. Specifically painful swelling of the fingers joints, which may closely resemble rheumatoid arthritis, significant difference is the absence of joint stiffness.

Kellgren JH 1952 Knee joint super laxity.

Catteneo ankylosis of elbow joint Clin Med Ital 1932, ns, 63: 324ff

1.3.3 Carpal tunnel syndrome and amyotrophy

Merck manual 1472

Decreased innervation, decrease in thenar eminence original cause tissue growth around the carpal tunnel. Diagrams needed. If possible photo-dissection/operation.

Median nerve compression advanced cases associated with a variable degree of atrophy. Tinels sign +ve.

Amyotrophy - wasting of the muscles commonly occurs in the forearms and lower legs and in the small muscles of the hand accompanied by abnormal sensory changes, poor prognosis. Also secondary to carpal tunnel syndrome.

1.3.4 Skin and adnexae

Pigmentation changes, pedunculated molluscum fibrosum. Nails frequently slight longitudinal cracks.Kho KM et al 1970 Heel pad thickness

Wright AD et al 1969 Skin folds thickness normal/acromegaly/cushing syndrome

Often the hands have a sodden appearance due to excessive sweating. Barrs AG 1892

Skin conditions in association are quite common, pigmentation may increase giving the skin an olive tint.

Cutis verticis gyrata and cutis verticis laxa

A considerable increase in scalp skin folds often occurs which may be seen as many furrowed ridges on the forehead or less frequently over the whole scalp. (Series of pictures)

Dott NM and Bailey P 1925

Sisson JR 1926

Weber FP 1928 Drawings Cowan 1893 McDowell 1893

Weber FP & Atkinson FRB 1928 Unilateral

Toshkov D 1937

Lundberg PO et al 1971 mot a very good example

Tasa Burotani et al 1977 + surgical treatment

Rosenthal Uncertain acr

1.3.5 Nasal and oropharyngeal changes

Coarsened partly due to bony changes and increase in soft tissues. Thick lips and coarse hair.

Larynx

Changes in the voice are reported frequently with the voice becoming thick and husky, male and female alike, and always monotonous as no tonal variety is possible when the larynx is enlarged (Jackson C 1918) Pictures and description)

The quality and pitch of voice deteriorated ‘ lower by two notes’ Whyte Mackie, J. 1893

Respiration difficult due to deformation voice thick and husky always monotonous Appleyard 1892.

Tongue, palate, tonsils and uvula - all of these enlarge to a variable extent most prominent, or protruding of these is the tongue which can enlarge to such an extent that breathing is very difficult and the jaw is dislocated. (Post-mortem, Chalk O 1857). Animal experiments ( ) have shown the direct relationship to increase in growth hormone to increased tongue size.

Geddes 1909/11 Tongue changes in size autopsy view.

Cf Atkinson 1934

Curti OP 1933 La Prensa Méd. Buenos Aires 20: 2704 ff. Tonsils enlarged

Cattaneo, L. 1932 Clin Med Ital, ns 63, 324 ff

Skeletal changes

There is no uniform extent to which skeletal features change. The variability is not only with progression of the disease but varies from person to person with different areas showing the greatest prominence.

The overall skeletal changes produce a characteristic picture in the middle and late stages of acromegaly. Classifications of the deformity have been attempted (Launois & Roy 73). Here however we will primarily look at the gross individual changes in bones as the morphology alters (1.5) with the combination of skeletal and soft tissues changes.

1.4.1 Skull changes

1.4.2 Chest and spine

1.4.3 Extremities, upper and lower limbs

1.4.4 Other e.g. Osteophytes and pisiform bones.

Summary of skeletal changes

• Skull
  • Elongation of facial bones
  • Supra-orbital bosses
  • Prognathism
  • Jaw changes
  • Skull vault
  • Erosion of sella turcica and associated changes in craniopharyngeal canal
  • Nasal bones
  • Sinuses enlarged etc.
• Chest and spine
  • Sternal protrusion (Punch like chest, respiration difficult)
  • Enlargement of rib cage
  • Kyphosis
  • Ossification of cartilage
• Extremities
  • Phalangeal tufting
  • Osteophyte formation

Riggs BL et al The nature of the metabolic bone disorder on acromegaly. J Lab Clin Med 1971; 78: 822-3. Barnes Med Lib

“ The data indicate that, in acromegaly, bone width increases and cortical bone mass is maintained or increases but trabecular bone is lost. This pattern suggests a redistribution of bone rather than a loss such as is seen in osteoporosis. The pattern is reminiscent of the normal changes that occur during adolescence with the restraint that radial bone growth can occur but linear growth cannot after epiphyseal closure.”

1.4.1 Skull changes

Prognathism

Protrusion of the lower jaw this is due mainly to the stimulation of the latent chondroblasts in the mandibular condyle, not seen if onset of acromegaly is after the age of 35. (Ramus)

In some cases the bones of the fingers show a decided increase in length trough participation of the epiphyses if not closed. Radiological interpretation. 1St X-ray sella. Date onset by changes in old skeletons?

Sternberg M 1899 re: Jaws of acromegalic skulls, pre and post protrusion

Dott MM & Bailey P 1925 Teeth/casts

Furnivall P 1898 Jaw

Bell 1919 Separation of teeth, prognathism of face

Cushing H 1927 Progressive change in jaw and prognathism

Korkhaus G 1933

Knaggs RL 1935 Jaw compared to normal acromegalic with teeth

Atkinson FR 1938

Camitta FD et al 1969 Facial changes prognathism

Supraorbital bosses

Burton CF 1921 Supraorbital bosses

Also Knaggs RL 1935

Calvaria and sella turcica

Atkinson FRB 1938 compared to normal.

1.4.2 Chest and spine

Knaggs RL 1935 Rib cage

1.4.3 Extremities, upper and lower limbs

1.4.4 Other e.g. Osteophytes and pisiform bones.

Joints formation of spurs, exostoses. PM pictures - pisiform bones etc.

Gross features

the progression of the disease with time produces the classic acromegalic facies and body morphology. The extent of deformity in the acromegalic produces similar features but with many variants. The series of illustrations which follow show the changes with time, from simple before and after to successive pictures with age in acromegalics and acromegalic giants.

(Cf Lewis A )

The differences with normal are seen by these comparisons. The two cases of uniovular twins also]help to show these changes. (cf 1.2)

Briggs JH 1959 Uniovular twins (Not very good here)

Yealland LR 1938 Acr + Kyphosis

Daughaday W et al 1950 Moderate acr.

Gibson GA 1899

Geddes AC 1909, 1911

Complete series of photographs over time together with autopsy.

Changes in secondary sexual characteristics

Hormonal changes in both male and female affect the gonads, adrenal gland, breast tissues to occasionally alter the appearance, cf 1.1. The tendency is to masculinization of women and feminization of men.

Summary of changes

Women Men Amenorrhea

Lactation

Virilism

Hirsutism

General female features coarsen as their bone structure is normally smoother with less musculature. Gynaecomastia (May be painful or unilateral)Simpson L 1937 Virilism

Northfield DWC 1949 Hirsutism

Briggs JH Gynaecomastia

Hedderich 1909

Cushing 1912

Erdheim J 1931 Virchow Arch path Anat 281: 197

Lactation testicles and prostate atrophied

Nechst Ovaries atrophied

Binet 19334 Bull Soc d’Obstet et Gyn 23: 422 Enlarged genitalia.

Effect on internal organs - Everything O'Megaly

Cardiomegaly growth disproportionate to the general tissue growth. Reports of massive cardiac growth.

Vagina elongated and patulous cf experiments with dogs and growth hormone. Uterus small and atrophied.

Megrectum X-rays Bizes - Atkinson 1931-34.

Thymus present/absent stats

Splanchnomegaly see Henrot 1882.

Splenomegaly.

Effect of changes in tumour size

Tumour size comparison

Effect of erosion - X-rays

Sight deformation of - squint/visual fields.

Squint Before and after Sternberg, M 1899

Sella turcica before and after.

Classic headache bilateral - distention of pituitary fossa. Unrelated to environmental or physical condition.

Acromegaly and pregnancy

". . . had not menstruated for two months and thought she was pregnant." 26 years old married for 4 years, Banks I 1897.

Cross-reference to Weiri "no corpore menses"

Comments from Atkinson 1935 and 1938.

Schnur M 1933

Signs of acromegaly ceased to progress after 6 months, the patient married and bore 3 children.

Kemény E 1936

Described a case in a woman who gave birth to a child six years later and died or puerperal sepsis. Autopsy revealed an eosinophilic adenoma of the pituitary gland. Pregnancy after acromegaly has developed is not uncommon.

Bringle CG 1937

The interest in Bringle's case ;lies in the fact that the pituitary tumour was removed and three years later, the woman became pregnant and gave birth to a healthy child.

Kloppner 1939 Pregnancy in acromegalic of 9 years duration.

Sturma J 1949 Twin pregnancy in acromegalic.

Pérez-Soler J 1950, Jackson I 1943, Abelove WA 1954, Finkler RS 1954, Greenblatt, RB 1956, Binet 1934, ?Erdheim 1931, Hecht 1934.