174
FAMILIAL
CONSTITUTIONAL
PRECOCIOUS
PUBERTY
IN A BOY THREE YEARS OF AGE
Report
of a Case
By EDWARD
A.
MORTIMER, JR., M.D.#{176}Boston
A
CCORDING to Wilkins,1 precociouspu-berty in boys is best classified into two
main groups, true precocity or complete
type, and vinilism or incomplete type. True
precocious puberty includes those cases
induced by the normal pituitary-gonadal
route. One form of true precocious puberty
occurs secondary to intracranial pathology
such as hydrocephahus, hypothalamic
he-sions and the controversial pineal lesions.
The other subdivision of true precocious
puberty is composed of those cases for
which no obvious cause can be found and
are thought to result simply from an early
initiation of normal pituitary hormonal
changes of puberty. These are usually
re-ferned to as instances of constitutional or
idiopathic precocious puberty. The second
main group of precocious puberty in boys
is composed of cases resulting from a
pni-many hormonal hypersecretion of the
go-nads or adrenals, without pituitary or
cen-tnal initiation, the so-called incomplete type,
or virilism. Included in this category are
cases with mascuhinization secondary to
adrenal hyperplasia and tumors, and
en-docnine testicular tumors.
In the constitutional or idiopathic group
are included the rather rare cases of familial
precocity. A search of the literature reveals
nine previously reported families. Stone2
in 1852 described the case of a four year old
boy with advanced sexual and physical
de-velopment whose father had been similianly
affected, and had first engaged in coitus at
From the Department of Pediatrics, Harvard Medical School, and the Children’s Medical Center, Boston.
(Received for publication July 13, 1953.)
0 Present address: Department of Pediatrics and
Contagious Diseases, Cleveland City Hospital, Cleveland.
8 years of age. Reuben and Manning3 cited
a similar case of a father and son, reported
by Durkee, and mentioned Machell’s
de-scription of another family. In 1940
Signist4 reported two brothers, aged 6 and
8 years,
with precocious
sexual and physicaldevelopment. Ore!5 in 1928 cited Bauer’s
case, and mentioned two brothers described
by S. Gross. Rush6 and others in 1937
ne-ported two brothers who developed
pu-bertal changes at 18 months and 3 years.
The father of these two had mature sexual
development at five, and in the four
preced-ing generations there were five similar
in-dividuals. Engstnom and MunsonT in 1951
described the case of a father and his two
Sons similarly affected. More recently,
J
acobsen and Macklin8 reported fivegenera-tions of a large family in which there were
27 instances of male precocity. Dr. Nathan
Talbot9
told
the author
of a case which hehad recently seen of a three year old who
first developed pubic hair at 10 months of
age. This boy’s father, uncle and
great-uncle, and three male cousins were likewise
affected. This boy was markedly advanced,
both sexually and physically. His bone age
was seven years, and testicular biopsy
showed active spermatocytogenesis. Urinary
17 ketosteroid excretion 1.058 mg. in 24
hours, urinary gonadotropic hormone was
less than three mouse units in 24 hours.
Because of the rarity of familial
con-stitutional precocity, the following, believed
to the tenth known family, is of interest.
CASE REPORT
This 39I2 yr. old boy, an only child, seemed
entirely normal until 18 mo. of age at which
time deepening of his voice and more rapid
growth than his playmates were noted by his
inter-9
1
1
‘1k
1
#{149}PATIENT
#{149}‘ INVOL.VeO MALES
d’
NORMAL MALES?
$OMAL FEMALESF1G. 1. Family tree.
FAMILIAL CONSTITUTIONAL PRECOCIOUS PUBERTY 175
mittcntly interested in women and girls 8 to
9 yr. and older. Also at about 2 yr., his penis was noted to be gradually enlarging, and about
3 to 4 mo. later pubic hair appeared in
increas-ing amounts. Commencing at about 23 yr.
erections of increasing frequency were
ob-served, but were unassociated with ejaculations. A light fuzz was noted at his tipper lip at about 3 yr. He frequently handled his genitalia but
never actually masturbated. No acne had been
seen. His energy was unusual and his appetite voracious. Motor amid mental development had
been within normal limits and there had been no illnesses.
The family history was remarkable iii that
the mother’s paternal grandfather and uncle,
and 3 out of 8 male cousins developed similar pubertal changes before the age of 3 yr. (Fig.
1). In addition, it was recalled that the mother’s
grandfather had known that this trait had run in his family for some generations, but full details were no longer available. None of the
females in the family had experienced prcco-cious changes. In tile involved males, short stature had been the rule as compared to the
normal members of the family. As adults, the 5
affected males ranged between 4’lO” and 5’3”
tall; other than short stature, there was no
his-tory of difficulties attributable to this trait in
adult life.
On physical examination, the child was large
with a general body contour suggesting that of
a maturing male (Fig. 2). Blood pressure was
normal. Weight was 23.6 kg., well over the
ninety-seventh percentile for his age, and at the
fiftieth percentile for 63 yr. old boys. His height was 112.5 cm., well over the
ninety-seventh percentile for his age, and at the fiftieth
percentile for 6 yr. old boys. (These percentile
estimates are derived from the anthropometric charts of the Harvard Medical School and Harvard School of Public Health.)
His face demonstrated the angular bony
fea-tures of an adolescent, and his shoulders were
broad. Muscular development was prominent, and his voice was low-pitched. Acne was not present. There was a small amount of fine
blond, axillary hair, but no chest or unusual
facial hair. The genitalia were enlarged, though not to adult size. His penis at times was noted
to be semiturgid. There was a small amount of soft, dark pubic hair. His testes appeared
larger than normal, measuring 2.2 by 1.5 cm. bilaterally, and were without palpable nodules
or masses. Rectal examination disclosed a pros-tate gland which was more prominent than
usual for his age; otherwise, his physical
cx-amination was normal.
Pertinent laboratory examinations included a
normal fasting blood sugar, NPN, and serum
chloride. A spinal fluid examination was normal.
An adrenalin eosinophihe test using 0.28 cc.
of 1 : 1000 adrenalin showed a 73% fall in 4
hr. Prostatic massage and smear of the urethral
discharge failed to reveal spermatozoa. A 24
per-176
EDWARD
A. MORTIMER,
JR.
formed in the Laboratories of the Burnham
Memorial Hospital for Children at the
Massa-chusetts General Hospital was reported as 0.7 mg., which was thought to be only slightly elevated for his age. Urinary gonadotropic
hormone analysis performed in the Biological Laboratories of the Massachusetts General Hos-pital was reported at less than 3 mouse units!
24 hr. Skull RGs were normal except for
dohichocephaly. His bone age was estimated to be 7 yr. by rocntgenographic examination.
Intravenous pyclogram was normal, as was an
electroencephalogram. Gross visual fields were
apparently normal. Psychologic examination
performed by Dr. Edith Meyer determined his intellectual level to be about 36 to 42 mo.
See-tions of a testicular biopsy showed abundant
primary spermatocytes with occasional mitoses
but only a rare spcrmatid. Interstitial cells were present in moderate numbers, though not as
numerous as in an adult male. The sections were interpreted as being consistent with
pitui-tary stimulation.
The patient has not been seen subsequently; however, communication with the parents pro-vided the information that at the age of 52
yr., he had reached 140 cm. in height and
weighed 36.4 kg. His strength and energy were
remarkable. He had developed acne and mas-turbation had been noted. Because of the
strong family history and the failure to
demon-strate any other responsible lesion, it was felt the boy reported a case of constitutional or idiopathic precocious puberty of the familial
type. It was felt that no therapy was available
other than that directed more at the psychologic problems, which for obvious reasons would
tend to arise in such a situation.
SUMMARY
A case of familial constitutional
preco-cious puberty in a boy of 3 years is reported
with a brief review of the nine previously
described families. In addition, an eleventh
instance is mentioned.
ACKNOWLEDGMENT
The author wishes to acknowledge the
constructive criticism and suggestions
offered by Drs. Nathan Talbot and Charles
D. Cook, and to express appreciation to
Dn. Talbot for permission to describe his
case.
FIG. 2. Patient, aged 37’i2 yr., compared to normal boy, aged 21%2 yr.
REFERENCES
1. Wilkins, L., Diagnosis and Treatment of
Endocrine Disorders in Childhood and
Adolescence, Springfield, Ill., Charles C
Thomas, Publisher, 1950.
2. Stone, R. K., Extraordinary precocity in
de-velopmcnt of male sexual organs and
muscular system of a child four years old, Am.
J.
M. Sc. 24:561, 1852.3. Reuben, M. S., and Manning, G. R.,
Pre-cocious puberty, Arch. Pediat. 39:769,
1922.
4. Sigrist, V. E., tYber drei Falle von genuiner
und einer Fall von zerebraler Pubertas
Praecox, Ann. paediat. 155:84, 1940.
5. Orel,
J.
L., Pubertas praecox, Ztschr. f.Konstitutionslehre 13:694, 1928.
6. Rush, H. P., Bilderback,
J.
B., Shocum, D.,and Rogers, A., Pubertas praecox
(macro-genitosomia), Endocrinology 21:404,
1937.
7. Engstrom, W. W., and Munson, P. L. ,
Pre-cocious sexual and somatic development
in boys due to constitutional and
endo-crine factors, Am.
J.
Dis. Child. 81:179, 1951.8. Jacobsen, A. W., and Mackhin, Madge T.,
FAMILIAL CONSTITUTIONAL PRECOCIOUS PUBERTY 177
300 Longwood Avenue
family with 27 affected members,
PEDI-ATRICS 6:682, 1952.
9. Talbot, N. B., Personal communication to the author.
SPANISH ABSTRACT
Pubertad
Precoz
Constitucional
Familiar
en un
Ni#{241}o
de
Tres
A#{241}os
La pubertad precoz en los ni#{241}osse clasifica en dos grupos pnincipales de acuerdo con Wilkins : el tipo completo o verdadero y el tipo
incomplcto o vinihismo. El primero abarca los
casos producidos por ha via hormonal pituitania-gonadiana, los secundarios a patologIa
intracra-ncana y por Oltimo aqu#{233}lhos de causa no
definida considerados simplemente como
re-suhtados de una iniciaciOn temprana de los
cambios hormonales hipofisiarosis de ha pubertad (pubertad precoz constitucional o idiop#{225}tica);
el segundo grupo comprende casos de
hiper-sccreci#{243}n de ha gonadas o suprarrenales sin
intervenci#{243}n central o hipofisiaria, como por ejemplo, en ha hiperplasia o los tumores suprar-renales y los tumores testicuhares endOcrinos.
En el grupo idiop#{225}tico o constitucional se incluycn los pocos casos de precocidad familiar,
de los que hasta ha fecha se han reportado 9 famihias. Este artIculo presenta ha d#{233}cima
estudiada y reportada y menciona la Ondecima
(
vista por el Dr. Talbot). Es ha rareza de estepadecimiento familiar y constitucional ho que
obhiga al autor a publicar este nuevo caso; se
refiere a un nino de tres aflos dos meses de
edad, cuyo desarrollo puberal se inici#{243}desde los dos aflos, y cuyos antecedentes refieren
apanici#{243}n de pubertad precoz en ha abuelo
materno, Un tb y tres pnimos, todos desdc antes
de los tres afios de edad; el abuclo materno
seflala que esta caracterIstica se comentaba en
su familia como existiendo durante vanias
gencraciones pero sin observarse en miembros
femeninos.
El autor hace una descripci#{243}n dcl examen fIsico del fliflO; los datos de laboratorio fueron normales en su mayorIa; los 17-ketoesteroides
se encontraron higeramente elevados para su
edad, has gonadotrofinas urinarias menos de 3
unidades rata por 24 horas, ha edad #{243}sease
consider#{243} de siete anos y el examen psicoh#{243}gico
para una edad de 36 a 42 meses. La biopsia
testicular mostr#{243} abundantes espermatocitos
con mitosis ocasionales, muy escasos
esperma-tozoides y c#{233}lulasintersticiales en cantidades
moderadas; estos datos se interpretaron como
debidos a estimulaci#{243}n hipofisiaria. A los 5 a#{241}osdos meses, el mflo media 1.40 metros de
altura, pesaba 36.4 kilogramos y se comportaba
corno un verdadero adolescente. No se sujet#{243}
